igg1  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc igg1
    Top 3 molecular networks of cytokine and chemokine secretome in human astrocytes.
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    1) Product Images from "Human Astrocytes: Secretome Profiles of Cytokines and Chemokines"

    Article Title: Human Astrocytes: Secretome Profiles of Cytokines and Chemokines

    Journal: PLoS ONE

    doi: 10.1371/journal.pone.0092325

    Top 3 molecular networks of cytokine and chemokine secretome in human astrocytes.
    Figure Legend Snippet: Top 3 molecular networks of cytokine and chemokine secretome in human astrocytes.

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    igg1  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc igg1
    Top 3 molecular networks of cytokine and chemokine secretome in human astrocytes.
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    1) Product Images from "Human Astrocytes: Secretome Profiles of Cytokines and Chemokines"

    Article Title: Human Astrocytes: Secretome Profiles of Cytokines and Chemokines

    Journal: PLoS ONE

    doi: 10.1371/journal.pone.0092325

    Top 3 molecular networks of cytokine and chemokine secretome in human astrocytes.
    Figure Legend Snippet: Top 3 molecular networks of cytokine and chemokine secretome in human astrocytes.

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    perk  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc perk
    UPR activation regulated the synthesis of NPCs through the <t>PERK</t> <t>and</t> <t>IRE1-</t> α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.
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    1) Product Images from "The Role of Unfolded Protein Response in Human Intervertebral Disc Degeneration: Perk and IRE1- α as Two Potential Therapeutic Targets"

    Article Title: The Role of Unfolded Protein Response in Human Intervertebral Disc Degeneration: Perk and IRE1- α as Two Potential Therapeutic Targets

    Journal: Oxidative Medicine and Cellular Longevity

    doi: 10.1155/2021/6492879

    UPR activation regulated the synthesis of NPCs through the PERK and IRE1- α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.
    Figure Legend Snippet: UPR activation regulated the synthesis of NPCs through the PERK and IRE1- α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.

    Techniques Used: Activation Assay, Expressing, Transfection, Real-time Polymerase Chain Reaction, Western Blot

    igg1  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc igg1
    Igg1, supplied by Cell Signaling Technology Inc, used in various techniques. Bioz Stars score: 95/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    igg  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc igg
    Igg, supplied by Cell Signaling Technology Inc, used in various techniques. Bioz Stars score: 95/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    anti mouse igg hrp  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc anti mouse igg hrp
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    hrp conjugate  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc hrp conjugate
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    hrp conjugated goat anti mouse igg1  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc hrp conjugated goat anti mouse igg1
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    igg1  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc igg1
    List of primary antibodies used for immunocytochemistry.
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    1) Product Images from "Free Fatty Acid Palmitate Impairs the Vitality and Function of Cultured Human Bladder Smooth Muscle Cells"

    Article Title: Free Fatty Acid Palmitate Impairs the Vitality and Function of Cultured Human Bladder Smooth Muscle Cells

    Journal: PLoS ONE

    doi: 10.1371/journal.pone.0041026

    List of primary antibodies used for immunocytochemistry.
    Figure Legend Snippet: List of primary antibodies used for immunocytochemistry.

    Techniques Used: Immunocytochemistry

    anti goat igg  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc anti goat igg
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    igg4 igg1  (Cell Signaling Technology Inc)


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    Cell Signaling Technology Inc igg4 igg1
    Disease antigens implicated in Heymann nephritis and membranous nephropathy.
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    1) Product Images from "Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment"

    Article Title: Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment

    Journal: Frontiers in Immunology

    doi: 10.3389/fimmu.2022.1036249

    Disease antigens implicated in Heymann nephritis and membranous nephropathy.
    Figure Legend Snippet: Disease antigens implicated in Heymann nephritis and membranous nephropathy.

    Techniques Used: Expressing, Activation Assay, Binding Assay, Migration

    Mechanism of podocyte injury in Heymann nephritis (A) and primary membranous nephropathy (B) Created with BioRender.com . GBM, glomerular basement membrane; ROS, reactive oxygen species; cPLA2, cytosolic phospholipase A2; PGE2, prostaglandin E2; TxA2, thromboxane A2; COX, cyclo-oxygenase; AA, arachidonic acid; ER, endoplasmic reticulum; RAP, receptor associated protein; Treg, regulatory T cell; Th1, CD4 + T helper-1 cell; Tfh, CD4 + T follicular helper cell; FH, fumarate hydratase; WT-1, Wilms tumor-1; PLA2R, M-type phospholipase A2 receptor 1; C3aR, C3a receptor; C5aR, C5a receptor; MBL, mannan-binding lectin; MASP, mannan-binding lectin serine protease; ZO-1, zonula occludens-1; THSD7A, thrombospondin type-1 domain-containing protein 7A; NELL1, neural epidermal growth factor-like 1 protein; Sema3B, semaphorin 3B; PCDH7, protocadherin 7; HTRA1, high temperature requirement A serine peptidase 1; NTNG1, netrin G1; Th2, CD4 + T helper-2 cell; Th17, CD4 + T helper-17 cell; IFN-γ, interferon-γ; *cognate antigen for anti-NELL1, anti-Sema3B, anti-PCDH7, anti-serine protease HTRA1, and anti-NTNG1 autoantibodies respectively. (A) : 1. In Heymann nephritis, anti-Fx1A antibodies bind primarily to megalin on podocytes and activate the classical complement pathway (via the IgG2b subclass). 2. Anti-RAP antibodies are also detected and may represent epitope spreading due to the association between megalin and RAP, which assists the transport of megalin from ER to cell surface. 3. Complement activation may be potentially exacerbated by binding of anti-Fx1A antibodies to complement regulatory proteins Crry and CD59. 4. Sublethal C5b-9 injury causes intracellular calcium influx, activating cPLA2, which hydrolyzes membrane phospholipids of the podocyte, ER and nuclear envelope. This causes ER stress, generation of ROS, disruption of the slit diaphragm protein nephrin, and release of AA with subsequent COX-mediated generation of prostanoids (PGE2, TxA2) that increase glomerular filtration pressure, exacerbating proteinuria. Glomerular IgG and complement deposition attract glomerular infiltrates of CD8 + T cells, Th1 cells, and macrophages, potentially via the IgG Fc receptor and anaphylatoxins C3a/C5a. 5. Autoantibody production in Heymann nephritis is at least in part dependent on Qa-1-expressing Tfh cells, which are inhibited by CD8 + Tregs. (B) : 1. In primary membranous nephropathy (PMN), autoantibodies are predominantly directed against PLA2R, and 2. less commonly against THSD7A, 3. NELL1, PCDH7, serine protease HTRA1 and NTNG1, except in pediatric PMN where Sema3B is the most common podocyte antigen targeted by autoantibodies. 4. Increased B cells and Tfh cells are observed, which interact in the germinal center of lymph nodes to induce differentiation of B cells into high-affinity antibody-producing plasma cells. Autoantibodies in PMN are primarily of the IgG4 subclass, potentially due to Th2-mediated IL-4 production. Loss of tolerance to podocyte antigens such as PLA2R may be due to loss of thymus-derived podocyte antigen-specific Tregs. 5. Glycosylated anti-PLA2R IgG4 bind the MBL/MASP-1/2 complex to activate the lectin complement pathway. 6. This causes activation of C3aR and C5aR as well as deposition of C5b-9, which activates cathepsin L- and an aspartic protease-mediated proteolysis of the actin cytoskeleton protein synaptopodin and slit diaphragm protein NEPH1 respectively. Anti-PLA2R antibody-containing serum is also associated with reduced FH, impaired autophagy and reduced adhesion to the GBM, though it is unclear whether these effects are mediated via complement activation. 7. Impairment in autophagy results in internalization of nephrin and the actin cytoskeleton protein α-actinin-4. 8. Reduced FH leads to intracellular fumarate accumulation, which is associated with increased generation of ROS, reduced slit diaphragm protein ZO-1 and reduced transcription of WT-1, which normally activates the expression of podocyte proteins nephrin and podocalyxin. The mechanisms of podocyte injury of other autoantibodies associated with PMN remain incompletely understood.
    Figure Legend Snippet: Mechanism of podocyte injury in Heymann nephritis (A) and primary membranous nephropathy (B) Created with BioRender.com . GBM, glomerular basement membrane; ROS, reactive oxygen species; cPLA2, cytosolic phospholipase A2; PGE2, prostaglandin E2; TxA2, thromboxane A2; COX, cyclo-oxygenase; AA, arachidonic acid; ER, endoplasmic reticulum; RAP, receptor associated protein; Treg, regulatory T cell; Th1, CD4 + T helper-1 cell; Tfh, CD4 + T follicular helper cell; FH, fumarate hydratase; WT-1, Wilms tumor-1; PLA2R, M-type phospholipase A2 receptor 1; C3aR, C3a receptor; C5aR, C5a receptor; MBL, mannan-binding lectin; MASP, mannan-binding lectin serine protease; ZO-1, zonula occludens-1; THSD7A, thrombospondin type-1 domain-containing protein 7A; NELL1, neural epidermal growth factor-like 1 protein; Sema3B, semaphorin 3B; PCDH7, protocadherin 7; HTRA1, high temperature requirement A serine peptidase 1; NTNG1, netrin G1; Th2, CD4 + T helper-2 cell; Th17, CD4 + T helper-17 cell; IFN-γ, interferon-γ; *cognate antigen for anti-NELL1, anti-Sema3B, anti-PCDH7, anti-serine protease HTRA1, and anti-NTNG1 autoantibodies respectively. (A) : 1. In Heymann nephritis, anti-Fx1A antibodies bind primarily to megalin on podocytes and activate the classical complement pathway (via the IgG2b subclass). 2. Anti-RAP antibodies are also detected and may represent epitope spreading due to the association between megalin and RAP, which assists the transport of megalin from ER to cell surface. 3. Complement activation may be potentially exacerbated by binding of anti-Fx1A antibodies to complement regulatory proteins Crry and CD59. 4. Sublethal C5b-9 injury causes intracellular calcium influx, activating cPLA2, which hydrolyzes membrane phospholipids of the podocyte, ER and nuclear envelope. This causes ER stress, generation of ROS, disruption of the slit diaphragm protein nephrin, and release of AA with subsequent COX-mediated generation of prostanoids (PGE2, TxA2) that increase glomerular filtration pressure, exacerbating proteinuria. Glomerular IgG and complement deposition attract glomerular infiltrates of CD8 + T cells, Th1 cells, and macrophages, potentially via the IgG Fc receptor and anaphylatoxins C3a/C5a. 5. Autoantibody production in Heymann nephritis is at least in part dependent on Qa-1-expressing Tfh cells, which are inhibited by CD8 + Tregs. (B) : 1. In primary membranous nephropathy (PMN), autoantibodies are predominantly directed against PLA2R, and 2. less commonly against THSD7A, 3. NELL1, PCDH7, serine protease HTRA1 and NTNG1, except in pediatric PMN where Sema3B is the most common podocyte antigen targeted by autoantibodies. 4. Increased B cells and Tfh cells are observed, which interact in the germinal center of lymph nodes to induce differentiation of B cells into high-affinity antibody-producing plasma cells. Autoantibodies in PMN are primarily of the IgG4 subclass, potentially due to Th2-mediated IL-4 production. Loss of tolerance to podocyte antigens such as PLA2R may be due to loss of thymus-derived podocyte antigen-specific Tregs. 5. Glycosylated anti-PLA2R IgG4 bind the MBL/MASP-1/2 complex to activate the lectin complement pathway. 6. This causes activation of C3aR and C5aR as well as deposition of C5b-9, which activates cathepsin L- and an aspartic protease-mediated proteolysis of the actin cytoskeleton protein synaptopodin and slit diaphragm protein NEPH1 respectively. Anti-PLA2R antibody-containing serum is also associated with reduced FH, impaired autophagy and reduced adhesion to the GBM, though it is unclear whether these effects are mediated via complement activation. 7. Impairment in autophagy results in internalization of nephrin and the actin cytoskeleton protein α-actinin-4. 8. Reduced FH leads to intracellular fumarate accumulation, which is associated with increased generation of ROS, reduced slit diaphragm protein ZO-1 and reduced transcription of WT-1, which normally activates the expression of podocyte proteins nephrin and podocalyxin. The mechanisms of podocyte injury of other autoantibodies associated with PMN remain incompletely understood.

    Techniques Used: Wilms Tumor Assay, Binding Assay, Activation Assay, Filtration, Expressing, Derivative Assay

    Overview of the complement system. Created with BioRender.com . MBL, mannan-binding lectin; MASP, mannan-binding lectin serine protease; C4BP, C4b-binding protein; DAF, decay-accelerating factor; MCP, membrane cofactor protein; CR1, complement receptor 1; MAC, membrane attack complex; C3aR, C3a receptor; C5aR, C5a receptor; PMN, primary membranous nephropathy; PLA2R, M-type phospholipase A2 receptor 1; THSD7A, thrombospondin type-1 domain-containing protein 7A. The complement system consists of 3 pathways: classical pathway, lectin pathway and alternative pathway, which can be conceptually understood using 4A’s: attachment, activation, amplification, and attack (steps of complement activation in bold text below). In the classical pathway, complement C1q attaches to the Fc receptor of antigen-bound antibodies (IgG1, IgG3 and IgM in humans, and IgG2a and IgG2b in rodents). The lectin pathway is similar to the classical pathway where lectins (such as ficolins, MBLs or collectins) attach to carbohydrates on pathogens, activating MASP-1 and MASP-2 (analogous to C1r and C1s of the classical pathway), which cleave C4 and C2 to form C3 convertase (C4b2b). In the alternative pathway, small amounts of C3 are spontaneously activated (“C3 tickover”) due to a labile thioester bond, forming a C3b fragment that binds to factor B (B), which in turn is cleaved by factor D (D) to form the alternative pathway C3 convertase (C3bBb) that is stabilised by properdin (P), forming C3bBbP. Regardless of the pathway of activation, C3 convertase cleaves C3 into C3a and C3b, which amplifies alternative pathway activation whereby further factor B binds to C3b forming more C3 convertase. Apart from amplifying C3 convertase formation, C3b also acts as an opsonin and binds to C3 convertase to form C5 convertase (C4b2b3b and C3bBbC3bP), which cleaves C5 into C5a and C5b. C3a and C5a act as potent anaphylatoxins via their respective receptors (C3aR and C5aR). Complement attack is initiated by C5b sequentially binding C6, C7, C8, and C9 to form the MAC (C5b-9), which causes transmembrane pores that cause osmotic cell lysis or sublethal cell injury, activating internal cellular processes. The complement system is tightly regulated by proteins present in plasma (fluid-phase) and on cell surfaces including the podocyte (solid-phase). Fluid-phase regulators include C1q inhibitor (binds C1r/C1s and MASP-1/MASP-2 to prevent classical and lectin pathway activation), C4BP (binds C4b to prevent formation of the classical/lectin pathway C3 convertase), factor H (binds C3b to prevent formation of the alternative pathway C3 convertase), factor I (cofactor for factor H and MCP, which both inhibit C3 convertase formation), vitronectin (binds the C5b-7 complex to prevent MAC formation) and clusterin (binds C7, C8, C9 to prevent MAC formation). Solid-phase regulators include DAF (dissociates C2b from C4b and Bb from C3b to inactivate C3 convertase), MCP (binds C3b and C4b to prevent C3 convertase formation), CR1 (binds C3b and C4b to prevent C3 convertase formation) and CD59 (binds C8 and C9 to prevent MAC formation).
    Figure Legend Snippet: Overview of the complement system. Created with BioRender.com . MBL, mannan-binding lectin; MASP, mannan-binding lectin serine protease; C4BP, C4b-binding protein; DAF, decay-accelerating factor; MCP, membrane cofactor protein; CR1, complement receptor 1; MAC, membrane attack complex; C3aR, C3a receptor; C5aR, C5a receptor; PMN, primary membranous nephropathy; PLA2R, M-type phospholipase A2 receptor 1; THSD7A, thrombospondin type-1 domain-containing protein 7A. The complement system consists of 3 pathways: classical pathway, lectin pathway and alternative pathway, which can be conceptually understood using 4A’s: attachment, activation, amplification, and attack (steps of complement activation in bold text below). In the classical pathway, complement C1q attaches to the Fc receptor of antigen-bound antibodies (IgG1, IgG3 and IgM in humans, and IgG2a and IgG2b in rodents). The lectin pathway is similar to the classical pathway where lectins (such as ficolins, MBLs or collectins) attach to carbohydrates on pathogens, activating MASP-1 and MASP-2 (analogous to C1r and C1s of the classical pathway), which cleave C4 and C2 to form C3 convertase (C4b2b). In the alternative pathway, small amounts of C3 are spontaneously activated (“C3 tickover”) due to a labile thioester bond, forming a C3b fragment that binds to factor B (B), which in turn is cleaved by factor D (D) to form the alternative pathway C3 convertase (C3bBb) that is stabilised by properdin (P), forming C3bBbP. Regardless of the pathway of activation, C3 convertase cleaves C3 into C3a and C3b, which amplifies alternative pathway activation whereby further factor B binds to C3b forming more C3 convertase. Apart from amplifying C3 convertase formation, C3b also acts as an opsonin and binds to C3 convertase to form C5 convertase (C4b2b3b and C3bBbC3bP), which cleaves C5 into C5a and C5b. C3a and C5a act as potent anaphylatoxins via their respective receptors (C3aR and C5aR). Complement attack is initiated by C5b sequentially binding C6, C7, C8, and C9 to form the MAC (C5b-9), which causes transmembrane pores that cause osmotic cell lysis or sublethal cell injury, activating internal cellular processes. The complement system is tightly regulated by proteins present in plasma (fluid-phase) and on cell surfaces including the podocyte (solid-phase). Fluid-phase regulators include C1q inhibitor (binds C1r/C1s and MASP-1/MASP-2 to prevent classical and lectin pathway activation), C4BP (binds C4b to prevent formation of the classical/lectin pathway C3 convertase), factor H (binds C3b to prevent formation of the alternative pathway C3 convertase), factor I (cofactor for factor H and MCP, which both inhibit C3 convertase formation), vitronectin (binds the C5b-7 complex to prevent MAC formation) and clusterin (binds C7, C8, C9 to prevent MAC formation). Solid-phase regulators include DAF (dissociates C2b from C4b and Bb from C3b to inactivate C3 convertase), MCP (binds C3b and C4b to prevent C3 convertase formation), CR1 (binds C3b and C4b to prevent C3 convertase formation) and CD59 (binds C8 and C9 to prevent MAC formation).

    Techniques Used: Binding Assay, Activation Assay, Amplification, Lysis

    Complement system involvement in Heymann nephritis and membranous nephropathy.
    Figure Legend Snippet: Complement system involvement in Heymann nephritis and membranous nephropathy.

    Techniques Used: Staining, Binding Assay, Activation Assay, Expressing


    Figure Legend Snippet:

    Techniques Used: Recombinant

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    Cell Signaling Technology Inc igg1
    Top 3 molecular networks of cytokine and chemokine secretome in human astrocytes.
    Igg1, supplied by Cell Signaling Technology Inc, used in various techniques. Bioz Stars score: 95/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    UPR activation regulated the synthesis of NPCs through the <t>PERK</t> <t>and</t> <t>IRE1-</t> α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.
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    UPR activation regulated the synthesis of NPCs through the <t>PERK</t> <t>and</t> <t>IRE1-</t> α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.
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    Cell Signaling Technology Inc anti mouse igg hrp
    UPR activation regulated the synthesis of NPCs through the <t>PERK</t> <t>and</t> <t>IRE1-</t> α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.
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    UPR activation regulated the synthesis of NPCs through the <t>PERK</t> <t>and</t> <t>IRE1-</t> α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.
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    UPR activation regulated the synthesis of NPCs through the <t>PERK</t> <t>and</t> <t>IRE1-</t> α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.
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    UPR activation regulated the synthesis of NPCs through the <t>PERK</t> <t>and</t> <t>IRE1-</t> α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.
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    Disease antigens implicated in Heymann nephritis and membranous nephropathy.
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    Image Search Results


    Top 3 molecular networks of cytokine and chemokine secretome in human astrocytes.

    Journal: PLoS ONE

    Article Title: Human Astrocytes: Secretome Profiles of Cytokines and Chemokines

    doi: 10.1371/journal.pone.0092325

    Figure Lengend Snippet: Top 3 molecular networks of cytokine and chemokine secretome in human astrocytes.

    Article Snippet: 3 , Infectious Disease, Cell-To-Cell Signaling and Interaction, Cellular Growth and Proliferation , Calcineurin protein(s), CD3, collagen, CYP, estrogen receptor, Hdac, hemoglobin, Histone h4, Hsp27, Hsp70, Hsp90, Icam, Iga, IgG1, Igm, IL-6 , IL-8 , Immunoglobulin, Interferon alpha, Ldh, Mek, Nfat (family), Notch, P38 MAPK, p70 S6k, Pro-inflammatory Cytokine, Rap1, Rsk, Serine Protease, Sod, SRC (family), STAT5a/b, TNF , TSH, U1 snRNP , 1.00E-05.

    Techniques:

    UPR activation regulated the synthesis of NPCs through the PERK and IRE1- α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.

    Journal: Oxidative Medicine and Cellular Longevity

    Article Title: The Role of Unfolded Protein Response in Human Intervertebral Disc Degeneration: Perk and IRE1- α as Two Potential Therapeutic Targets

    doi: 10.1155/2021/6492879

    Figure Lengend Snippet: UPR activation regulated the synthesis of NPCs through the PERK and IRE1- α pathways. (a) The expression of PERK, ATF6, and IRE1- α proteins in degenerated and nondegenerated NP tissues was detected by IHC. Representative images are presented at the indicated magnifications. Scale bar, 50 μ m. Compared with the controlled group, the presence of PERK and IRE1- α was significantly increased in degenerated tissues, whereas ATF6 was similar. (b) The expression of ATF6, IRE1- α , and PERK was downregulated after being transfected with PREK, ATF6, and IRE1- α siRNA as assayed by real-time PCR. (c) The expression of Agg, Col2, and SOX9 was significantly increased after knockdown of PERK and IRE1- α than ATF6 as assessed by western blot. β -Actin was used as an internal control. The representative results were from three independent experiments. The error bars represent the SD from the mean values.

    Article Snippet: The primary antibodies were all rabbit anti-human against IRE1- α (monoclonal IgG 1/50; Cell Signaling Technology), PERK (monoclonal IgG 1/100; Cell Signaling Technology), and ATF6 (polyclonal IgG 1/100; Abcam).

    Techniques: Activation Assay, Expressing, Transfection, Real-time Polymerase Chain Reaction, Western Blot

    Disease antigens implicated in Heymann nephritis and membranous nephropathy.

    Journal: Frontiers in Immunology

    Article Title: Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment

    doi: 10.3389/fimmu.2022.1036249

    Figure Lengend Snippet: Disease antigens implicated in Heymann nephritis and membranous nephropathy.

    Article Snippet: PCDH7 , Brain, kidney tubule ( ) , Unclear in kidney. Cell signaling , 2% , IgG4 >> IgG1, IgG2, IgG3 , Yes (non-reducing) , Unclear , Trace C3 , 61 , 3:1 , Autoimmune disease (21%), malignancy (14%).

    Techniques: Expressing, Activation Assay, Binding Assay, Migration

    Mechanism of podocyte injury in Heymann nephritis (A) and primary membranous nephropathy (B) Created with BioRender.com . GBM, glomerular basement membrane; ROS, reactive oxygen species; cPLA2, cytosolic phospholipase A2; PGE2, prostaglandin E2; TxA2, thromboxane A2; COX, cyclo-oxygenase; AA, arachidonic acid; ER, endoplasmic reticulum; RAP, receptor associated protein; Treg, regulatory T cell; Th1, CD4 + T helper-1 cell; Tfh, CD4 + T follicular helper cell; FH, fumarate hydratase; WT-1, Wilms tumor-1; PLA2R, M-type phospholipase A2 receptor 1; C3aR, C3a receptor; C5aR, C5a receptor; MBL, mannan-binding lectin; MASP, mannan-binding lectin serine protease; ZO-1, zonula occludens-1; THSD7A, thrombospondin type-1 domain-containing protein 7A; NELL1, neural epidermal growth factor-like 1 protein; Sema3B, semaphorin 3B; PCDH7, protocadherin 7; HTRA1, high temperature requirement A serine peptidase 1; NTNG1, netrin G1; Th2, CD4 + T helper-2 cell; Th17, CD4 + T helper-17 cell; IFN-γ, interferon-γ; *cognate antigen for anti-NELL1, anti-Sema3B, anti-PCDH7, anti-serine protease HTRA1, and anti-NTNG1 autoantibodies respectively. (A) : 1. In Heymann nephritis, anti-Fx1A antibodies bind primarily to megalin on podocytes and activate the classical complement pathway (via the IgG2b subclass). 2. Anti-RAP antibodies are also detected and may represent epitope spreading due to the association between megalin and RAP, which assists the transport of megalin from ER to cell surface. 3. Complement activation may be potentially exacerbated by binding of anti-Fx1A antibodies to complement regulatory proteins Crry and CD59. 4. Sublethal C5b-9 injury causes intracellular calcium influx, activating cPLA2, which hydrolyzes membrane phospholipids of the podocyte, ER and nuclear envelope. This causes ER stress, generation of ROS, disruption of the slit diaphragm protein nephrin, and release of AA with subsequent COX-mediated generation of prostanoids (PGE2, TxA2) that increase glomerular filtration pressure, exacerbating proteinuria. Glomerular IgG and complement deposition attract glomerular infiltrates of CD8 + T cells, Th1 cells, and macrophages, potentially via the IgG Fc receptor and anaphylatoxins C3a/C5a. 5. Autoantibody production in Heymann nephritis is at least in part dependent on Qa-1-expressing Tfh cells, which are inhibited by CD8 + Tregs. (B) : 1. In primary membranous nephropathy (PMN), autoantibodies are predominantly directed against PLA2R, and 2. less commonly against THSD7A, 3. NELL1, PCDH7, serine protease HTRA1 and NTNG1, except in pediatric PMN where Sema3B is the most common podocyte antigen targeted by autoantibodies. 4. Increased B cells and Tfh cells are observed, which interact in the germinal center of lymph nodes to induce differentiation of B cells into high-affinity antibody-producing plasma cells. Autoantibodies in PMN are primarily of the IgG4 subclass, potentially due to Th2-mediated IL-4 production. Loss of tolerance to podocyte antigens such as PLA2R may be due to loss of thymus-derived podocyte antigen-specific Tregs. 5. Glycosylated anti-PLA2R IgG4 bind the MBL/MASP-1/2 complex to activate the lectin complement pathway. 6. This causes activation of C3aR and C5aR as well as deposition of C5b-9, which activates cathepsin L- and an aspartic protease-mediated proteolysis of the actin cytoskeleton protein synaptopodin and slit diaphragm protein NEPH1 respectively. Anti-PLA2R antibody-containing serum is also associated with reduced FH, impaired autophagy and reduced adhesion to the GBM, though it is unclear whether these effects are mediated via complement activation. 7. Impairment in autophagy results in internalization of nephrin and the actin cytoskeleton protein α-actinin-4. 8. Reduced FH leads to intracellular fumarate accumulation, which is associated with increased generation of ROS, reduced slit diaphragm protein ZO-1 and reduced transcription of WT-1, which normally activates the expression of podocyte proteins nephrin and podocalyxin. The mechanisms of podocyte injury of other autoantibodies associated with PMN remain incompletely understood.

    Journal: Frontiers in Immunology

    Article Title: Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment

    doi: 10.3389/fimmu.2022.1036249

    Figure Lengend Snippet: Mechanism of podocyte injury in Heymann nephritis (A) and primary membranous nephropathy (B) Created with BioRender.com . GBM, glomerular basement membrane; ROS, reactive oxygen species; cPLA2, cytosolic phospholipase A2; PGE2, prostaglandin E2; TxA2, thromboxane A2; COX, cyclo-oxygenase; AA, arachidonic acid; ER, endoplasmic reticulum; RAP, receptor associated protein; Treg, regulatory T cell; Th1, CD4 + T helper-1 cell; Tfh, CD4 + T follicular helper cell; FH, fumarate hydratase; WT-1, Wilms tumor-1; PLA2R, M-type phospholipase A2 receptor 1; C3aR, C3a receptor; C5aR, C5a receptor; MBL, mannan-binding lectin; MASP, mannan-binding lectin serine protease; ZO-1, zonula occludens-1; THSD7A, thrombospondin type-1 domain-containing protein 7A; NELL1, neural epidermal growth factor-like 1 protein; Sema3B, semaphorin 3B; PCDH7, protocadherin 7; HTRA1, high temperature requirement A serine peptidase 1; NTNG1, netrin G1; Th2, CD4 + T helper-2 cell; Th17, CD4 + T helper-17 cell; IFN-γ, interferon-γ; *cognate antigen for anti-NELL1, anti-Sema3B, anti-PCDH7, anti-serine protease HTRA1, and anti-NTNG1 autoantibodies respectively. (A) : 1. In Heymann nephritis, anti-Fx1A antibodies bind primarily to megalin on podocytes and activate the classical complement pathway (via the IgG2b subclass). 2. Anti-RAP antibodies are also detected and may represent epitope spreading due to the association between megalin and RAP, which assists the transport of megalin from ER to cell surface. 3. Complement activation may be potentially exacerbated by binding of anti-Fx1A antibodies to complement regulatory proteins Crry and CD59. 4. Sublethal C5b-9 injury causes intracellular calcium influx, activating cPLA2, which hydrolyzes membrane phospholipids of the podocyte, ER and nuclear envelope. This causes ER stress, generation of ROS, disruption of the slit diaphragm protein nephrin, and release of AA with subsequent COX-mediated generation of prostanoids (PGE2, TxA2) that increase glomerular filtration pressure, exacerbating proteinuria. Glomerular IgG and complement deposition attract glomerular infiltrates of CD8 + T cells, Th1 cells, and macrophages, potentially via the IgG Fc receptor and anaphylatoxins C3a/C5a. 5. Autoantibody production in Heymann nephritis is at least in part dependent on Qa-1-expressing Tfh cells, which are inhibited by CD8 + Tregs. (B) : 1. In primary membranous nephropathy (PMN), autoantibodies are predominantly directed against PLA2R, and 2. less commonly against THSD7A, 3. NELL1, PCDH7, serine protease HTRA1 and NTNG1, except in pediatric PMN where Sema3B is the most common podocyte antigen targeted by autoantibodies. 4. Increased B cells and Tfh cells are observed, which interact in the germinal center of lymph nodes to induce differentiation of B cells into high-affinity antibody-producing plasma cells. Autoantibodies in PMN are primarily of the IgG4 subclass, potentially due to Th2-mediated IL-4 production. Loss of tolerance to podocyte antigens such as PLA2R may be due to loss of thymus-derived podocyte antigen-specific Tregs. 5. Glycosylated anti-PLA2R IgG4 bind the MBL/MASP-1/2 complex to activate the lectin complement pathway. 6. This causes activation of C3aR and C5aR as well as deposition of C5b-9, which activates cathepsin L- and an aspartic protease-mediated proteolysis of the actin cytoskeleton protein synaptopodin and slit diaphragm protein NEPH1 respectively. Anti-PLA2R antibody-containing serum is also associated with reduced FH, impaired autophagy and reduced adhesion to the GBM, though it is unclear whether these effects are mediated via complement activation. 7. Impairment in autophagy results in internalization of nephrin and the actin cytoskeleton protein α-actinin-4. 8. Reduced FH leads to intracellular fumarate accumulation, which is associated with increased generation of ROS, reduced slit diaphragm protein ZO-1 and reduced transcription of WT-1, which normally activates the expression of podocyte proteins nephrin and podocalyxin. The mechanisms of podocyte injury of other autoantibodies associated with PMN remain incompletely understood.

    Article Snippet: PCDH7 , Brain, kidney tubule ( ) , Unclear in kidney. Cell signaling , 2% , IgG4 >> IgG1, IgG2, IgG3 , Yes (non-reducing) , Unclear , Trace C3 , 61 , 3:1 , Autoimmune disease (21%), malignancy (14%).

    Techniques: Wilms Tumor Assay, Binding Assay, Activation Assay, Filtration, Expressing, Derivative Assay

    Overview of the complement system. Created with BioRender.com . MBL, mannan-binding lectin; MASP, mannan-binding lectin serine protease; C4BP, C4b-binding protein; DAF, decay-accelerating factor; MCP, membrane cofactor protein; CR1, complement receptor 1; MAC, membrane attack complex; C3aR, C3a receptor; C5aR, C5a receptor; PMN, primary membranous nephropathy; PLA2R, M-type phospholipase A2 receptor 1; THSD7A, thrombospondin type-1 domain-containing protein 7A. The complement system consists of 3 pathways: classical pathway, lectin pathway and alternative pathway, which can be conceptually understood using 4A’s: attachment, activation, amplification, and attack (steps of complement activation in bold text below). In the classical pathway, complement C1q attaches to the Fc receptor of antigen-bound antibodies (IgG1, IgG3 and IgM in humans, and IgG2a and IgG2b in rodents). The lectin pathway is similar to the classical pathway where lectins (such as ficolins, MBLs or collectins) attach to carbohydrates on pathogens, activating MASP-1 and MASP-2 (analogous to C1r and C1s of the classical pathway), which cleave C4 and C2 to form C3 convertase (C4b2b). In the alternative pathway, small amounts of C3 are spontaneously activated (“C3 tickover”) due to a labile thioester bond, forming a C3b fragment that binds to factor B (B), which in turn is cleaved by factor D (D) to form the alternative pathway C3 convertase (C3bBb) that is stabilised by properdin (P), forming C3bBbP. Regardless of the pathway of activation, C3 convertase cleaves C3 into C3a and C3b, which amplifies alternative pathway activation whereby further factor B binds to C3b forming more C3 convertase. Apart from amplifying C3 convertase formation, C3b also acts as an opsonin and binds to C3 convertase to form C5 convertase (C4b2b3b and C3bBbC3bP), which cleaves C5 into C5a and C5b. C3a and C5a act as potent anaphylatoxins via their respective receptors (C3aR and C5aR). Complement attack is initiated by C5b sequentially binding C6, C7, C8, and C9 to form the MAC (C5b-9), which causes transmembrane pores that cause osmotic cell lysis or sublethal cell injury, activating internal cellular processes. The complement system is tightly regulated by proteins present in plasma (fluid-phase) and on cell surfaces including the podocyte (solid-phase). Fluid-phase regulators include C1q inhibitor (binds C1r/C1s and MASP-1/MASP-2 to prevent classical and lectin pathway activation), C4BP (binds C4b to prevent formation of the classical/lectin pathway C3 convertase), factor H (binds C3b to prevent formation of the alternative pathway C3 convertase), factor I (cofactor for factor H and MCP, which both inhibit C3 convertase formation), vitronectin (binds the C5b-7 complex to prevent MAC formation) and clusterin (binds C7, C8, C9 to prevent MAC formation). Solid-phase regulators include DAF (dissociates C2b from C4b and Bb from C3b to inactivate C3 convertase), MCP (binds C3b and C4b to prevent C3 convertase formation), CR1 (binds C3b and C4b to prevent C3 convertase formation) and CD59 (binds C8 and C9 to prevent MAC formation).

    Journal: Frontiers in Immunology

    Article Title: Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment

    doi: 10.3389/fimmu.2022.1036249

    Figure Lengend Snippet: Overview of the complement system. Created with BioRender.com . MBL, mannan-binding lectin; MASP, mannan-binding lectin serine protease; C4BP, C4b-binding protein; DAF, decay-accelerating factor; MCP, membrane cofactor protein; CR1, complement receptor 1; MAC, membrane attack complex; C3aR, C3a receptor; C5aR, C5a receptor; PMN, primary membranous nephropathy; PLA2R, M-type phospholipase A2 receptor 1; THSD7A, thrombospondin type-1 domain-containing protein 7A. The complement system consists of 3 pathways: classical pathway, lectin pathway and alternative pathway, which can be conceptually understood using 4A’s: attachment, activation, amplification, and attack (steps of complement activation in bold text below). In the classical pathway, complement C1q attaches to the Fc receptor of antigen-bound antibodies (IgG1, IgG3 and IgM in humans, and IgG2a and IgG2b in rodents). The lectin pathway is similar to the classical pathway where lectins (such as ficolins, MBLs or collectins) attach to carbohydrates on pathogens, activating MASP-1 and MASP-2 (analogous to C1r and C1s of the classical pathway), which cleave C4 and C2 to form C3 convertase (C4b2b). In the alternative pathway, small amounts of C3 are spontaneously activated (“C3 tickover”) due to a labile thioester bond, forming a C3b fragment that binds to factor B (B), which in turn is cleaved by factor D (D) to form the alternative pathway C3 convertase (C3bBb) that is stabilised by properdin (P), forming C3bBbP. Regardless of the pathway of activation, C3 convertase cleaves C3 into C3a and C3b, which amplifies alternative pathway activation whereby further factor B binds to C3b forming more C3 convertase. Apart from amplifying C3 convertase formation, C3b also acts as an opsonin and binds to C3 convertase to form C5 convertase (C4b2b3b and C3bBbC3bP), which cleaves C5 into C5a and C5b. C3a and C5a act as potent anaphylatoxins via their respective receptors (C3aR and C5aR). Complement attack is initiated by C5b sequentially binding C6, C7, C8, and C9 to form the MAC (C5b-9), which causes transmembrane pores that cause osmotic cell lysis or sublethal cell injury, activating internal cellular processes. The complement system is tightly regulated by proteins present in plasma (fluid-phase) and on cell surfaces including the podocyte (solid-phase). Fluid-phase regulators include C1q inhibitor (binds C1r/C1s and MASP-1/MASP-2 to prevent classical and lectin pathway activation), C4BP (binds C4b to prevent formation of the classical/lectin pathway C3 convertase), factor H (binds C3b to prevent formation of the alternative pathway C3 convertase), factor I (cofactor for factor H and MCP, which both inhibit C3 convertase formation), vitronectin (binds the C5b-7 complex to prevent MAC formation) and clusterin (binds C7, C8, C9 to prevent MAC formation). Solid-phase regulators include DAF (dissociates C2b from C4b and Bb from C3b to inactivate C3 convertase), MCP (binds C3b and C4b to prevent C3 convertase formation), CR1 (binds C3b and C4b to prevent C3 convertase formation) and CD59 (binds C8 and C9 to prevent MAC formation).

    Article Snippet: PCDH7 , Brain, kidney tubule ( ) , Unclear in kidney. Cell signaling , 2% , IgG4 >> IgG1, IgG2, IgG3 , Yes (non-reducing) , Unclear , Trace C3 , 61 , 3:1 , Autoimmune disease (21%), malignancy (14%).

    Techniques: Binding Assay, Activation Assay, Amplification, Lysis

    Complement system involvement in Heymann nephritis and membranous nephropathy.

    Journal: Frontiers in Immunology

    Article Title: Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment

    doi: 10.3389/fimmu.2022.1036249

    Figure Lengend Snippet: Complement system involvement in Heymann nephritis and membranous nephropathy.

    Article Snippet: PCDH7 , Brain, kidney tubule ( ) , Unclear in kidney. Cell signaling , 2% , IgG4 >> IgG1, IgG2, IgG3 , Yes (non-reducing) , Unclear , Trace C3 , 61 , 3:1 , Autoimmune disease (21%), malignancy (14%).

    Techniques: Staining, Binding Assay, Activation Assay, Expressing

    Journal: Frontiers in Immunology

    Article Title: Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment

    doi: 10.3389/fimmu.2022.1036249

    Figure Lengend Snippet:

    Article Snippet: PCDH7 , Brain, kidney tubule ( ) , Unclear in kidney. Cell signaling , 2% , IgG4 >> IgG1, IgG2, IgG3 , Yes (non-reducing) , Unclear , Trace C3 , 61 , 3:1 , Autoimmune disease (21%), malignancy (14%).

    Techniques: Recombinant