Journal: Redox Biology

Article Title: Repression of oxidative phosphorylation by NR2F2, MTERF3 and GDF15 in human skin under high-glucose stress

doi: 10.1016/j.redox.2025.103613

Figure Lengend Snippet: GDF15 biosynthesis is indispensable for human skin reconstruction . A) The effect of 100 nM GDF15 supplementation was determined using comparative proteomics on HDFs exposed to 12 mM glucose for 48H . The pathway analysis is shown as a bubble volcano plot (significant pathways with -logAdjPvalue>1.3 are shown. The pathways with blue dots are inhibited while pathways with orange dots are activated. The number of proteins detected for each pathway is represented by the diameter of each dot. Activation or inhibition was determined using the Z-score calculated by IPA Qiagen. B) Proteins of the Wound Healing Signaling, AMPK Signaling, Oxidative Phosphorylation or Protein Kinase A Signaling altered by the 12 mM glucose treatment are shown. C ) Human skin reconstruction was performed using fiboblasts expressing a shGDF15, wild-type fibroblasts exposed to 12 mM glucose or wild-type fibroblasts exposed to 12 mM glucose and supplemented with 2 nM GDF15. development. Macroscopic view is shown with a scale bar of 0.6 cm, D) Immunofluorescence study of HRS using DAPI marker (blue), Collagen I (yellow) and MKi67 (pink). Scale bar. 50 μM, N = 3. E , F ) Migration assay of HDF cultivated in 5.55 mM, 12 mM or 25 mM glucose and HDF cultivated in 12 mM glucose supplemented with 100 nM gdf15, HDF transfected with esiGDF15 or esiTFAM (N = 15). All data were expressed as the mean ± SEM. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001. Ordinary one-way ANOVA with Dunett's test correction was used for panel F.

Article Snippet: Expression plasmids in lentiviral vectors were purchased for MTERF3 Human Tagged ORF Clone (#RC201030L4, Origene) and GDF15 Human Tagged ORF Clone (#RC201295L2, Origene).

Techniques: Activation Assay, Inhibition, Phospho-proteomics, Expressing, Immunofluorescence, Marker, Migration, Transfection

Journal: Redox Biology

Article Title: Repression of oxidative phosphorylation by NR2F2, MTERF3 and GDF15 in human skin under high-glucose stress

doi: 10.1016/j.redox.2025.103613

Figure Lengend Snippet: cFOS and NR2F2 transcription factors mediate glucose-dependent repression of GDF15 in human dermis. A) Determination by Simple WES of the protein expression level of proGDF15 in wild-type HDF expressing shcontrol or shGDF15 (N = 3). B) Expression of GDF15 in the skin from human protein expression atlas from EMBL-EBI ( https://www.ebi.ac.uk ) which includes RNA-seq analyses from tissue samples of 122 human individuals, representing 32 different tissues. The results are expressed as TPM (Transcripts Per Kilobase Million). C) Quantification of GDF15 mRNA transcripts by taqman quantitative PCR in HDF, A549 and HEPG2 (N = 3). D) Quantification of GDF15 mRNA transcripts by taqman quantitative PCR in HDF, 786-O and SN005 cells (N = 3). E) ELISA-Based Quantification of GDF15 secretion in HDFs. HDFs were cultured under conditions of normal (5.5 mM) and high (12 mM) glucose concentrations during 48h. GDF15 levels in the culture supernatants were quantified using an enzyme-linked immunosorbent assay (ELISA) following the manufacturer's instructions. F) Quantification of GDF15 mRNA transcripts by taqman quantitative PCR in HDF grown in 5.55 mM, 12 mM or 25 mM glucose (N = 3). G) GDF15 promoter activity in HDF grown 24 h in DMEM with 5.55 mM,12 mM or 25 mM of glucose or 5.55 mM of galactose (N = 4). H) Dose-dependent relationship between GDF15 promoter activation and glucose concentration in the medium. I) GDF15 gene promoter sequence with identification of the binding site for the FOS transcription factor (Swiss Regulon Expasy). J) Quantification of FOS mRNA transcript by taqman quantitative PCR in HDF cultivated in 5.55 mM or 12 mM glucose (N = 3). K) Determination by Simple WES of FOS protein expression level in HDF cultivated in 5.55 mM or 12 mM glucose (N = 3). L-M) Determination by Simple WES of GDF15 protein expression level in HDF transfected with esiFOS (N = 3). N) Quantification of GDF15 mRNA transcript by taqman quantitative PCR in HDF transfected with esiNR2F2 (N = 3). O) Quantification of GDF15 mRNA transcript by taqman quantitative PCR in HDF expressing sgControl, sgRNA 1 targeting NR2F2 and sgRNA2 targeting NR2F2. Normalization of the data to GusB (β-glucuronidase), N = 3. P–S) Quantification of ATF3, ATF4, CHOP and P53 mRNA transcripts by taqman quantitative PCR in HDF expressing siCTRL and esiNR2F2 in 5.5 mM glucose or 12 mM glucose growth medium. Normalization of the data to GusB (β-glucuronidase), N = 3. T) Schematic representation of the NR2F2-MTERF3-GDF15 axis and its control on OXPHOS function in response to glucose stress. All data are expressed as the mean ± SEM. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001. Ordinary one-way ANOVA with Dunett's test correction was used for panel C, E and N. Unpaired t -test was used for panels A, B, H, I, J, K, L and M.

Article Snippet: Expression plasmids in lentiviral vectors were purchased for MTERF3 Human Tagged ORF Clone (#RC201030L4, Origene) and GDF15 Human Tagged ORF Clone (#RC201295L2, Origene).

Techniques: Expressing, RNA Sequencing, Real-time Polymerase Chain Reaction, Enzyme-linked Immunosorbent Assay, Cell Culture, Activity Assay, Activation Assay, Concentration Assay, Sequencing, Binding Assay, Transfection, Control

Journal: Redox Biology

Article Title: Repression of oxidative phosphorylation by NR2F2, MTERF3 and GDF15 in human skin under high-glucose stress

doi: 10.1016/j.redox.2025.103613

Figure Lengend Snippet: GDF15 inhibition by hyperglycemia or shRNA alters mitochondrial biogenesis. A) Metabolomic profile of HDF grown 48H in DMEM with 5.55 mM or 12 mM + 100 nM GDF15 of glucose and HDF expressing a shGDF15 cultivated in 5.55 mM glucose (N = 3). B) Oxygen consumption rate (OCR) was measured using the Seahorse XFe96. Routine respiration and uncoupled respiration (CCCP) were determined in HDF grown in 5.55 mM glucose and HDF expressing shGDF15 grown in 5.55 mM glucose or 5.55 mM glucose supplemented with 100 nM gdf15. C) Oxygen consumption rate (OCR) was measured using the Seahorse XFe96. Routine respiration and uncoupled respiration (CCCP) were determined in HDF grown in 5.55 mM glucose and supplemented with low doses of gdf15: 20pM, 80pM, 1 nM, 10 nM and 100 nM. D) Mitochondrial respiratory chain proteins (gene loci) specifically activated at the level of chromatin accessibility by GDF15 100 nM. E-H) Quantification of mRNA transcripts by taqman quantitative PCR for NR2F2, GDF15, MTERF3 and TFAM in HDF cultivated with 5.55 mM glucose or 5.55 mM glucose supplemented with 100 nM gdf15. Normalization of the data was performed to GusB (β-glucuronidase), N = 3. I-L) Quantification of mRNA transcripts by taqman quantitative PCR for GDF15, MAPK1, MAPK3, PGC1α (Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha) in HDF cultivated with 5.55 mM glucose supplemented with low doses of gdf15. Normalization of the data was performed to GusB (β-glucuronidase), N = 3 M) Quantification of TFAM mRNA transcripts by taqman quantitative PCR in HDF cultivated with 5.55 mM, 12 mM or 25 mM glucose or in HDF expressing shGDF15 grown in 5.55 mM glucose. Normalization of data was performed to GusB (β-glucuronidase), N = 3. N) Quantification of PGC1α mRNA transcript by taqman quantitative PCR in HDF cultivated with 5.55 mM, 12 mM or 25 mM glucose or in HDF expressing shGDF15 grown in 5.55 mM glucose. Normalization of the data to GusB (β-glucuronidase), N = 3. O) Quantification of PGC1α mRNA transcript by taqman quantitative PCR in HDF transfected with esiNR2F2. Normalization of data to GusB (β-glucuronidase), N = 3. P,Q) Quantification of the total Coenzyme Q10 (oxidized and reduced forms) in HDF cultivated with 5.55 mM, 12 mM or 12 mM glucose medium supplemented with 100 nM gdf15. Analysis was also performed in HDF expressing shGDF15 in 5.55 mM glucose. R) Quantification of TFAM in HDF cultivated with 5.55 mM glucose medium or medium supplemented with 20pM, 100 pM and 100 nM rGDF15. S) Summary of the regulatory network linking TFAM, PGC1α, COQ9 and COQ10. All data are expressed as the mean ± SEM. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001. Ordinary one-way ANOVA with Dunett's test correction was used for panel A, B, F, G, I-M, P–R. Unpaired t -test was used for panels E, H and O.

Article Snippet: Expression plasmids in lentiviral vectors were purchased for MTERF3 Human Tagged ORF Clone (#RC201030L4, Origene) and GDF15 Human Tagged ORF Clone (#RC201295L2, Origene).

Techniques: Inhibition, shRNA, Expressing, Real-time Polymerase Chain Reaction, Transfection

Journal: Frontiers in Immunology

Article Title: GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury

doi: 10.3389/fimmu.2025.1712741

Figure Lengend Snippet: LPS challenge induces time-dependent mitochondrial dysfunction and metabolic stress with compensatory GDF15 upregulation in liver injury (A) Temporal liver histopathology (H&E) post-LPS. Scale bar: 50 μm. (Time-resolved hepatic damage progression.) (B) Serum ALT/AST kinetics (n = 3). Data: mean ± SD. Study groups and individual replicates are identified in the figure key. ***p < 0.001. (Biomarker-confirmed hepatocyte injury.) (C) Progressive loss of hepatic UQCRC1 (mitochondrial complex III core subunit). β-actin: loading control.(Impaired mitochondrial electron transport.) (D) Time-elevated serum TNF-α, IL-6, and lactate in mice (n = 5). Study groups and individual replicates are identified in the figure key. ***p < 0.001. (Concomitant systemic inflammation and metabolic stress.) (E) Time-elevated cell culture supernatant TNF-α, IL-6, and lactate (n = 5). ***p < 0.001. (Concomitant inflammation and metabolic stress in cell culture system.) (F) Spatiotemporal GDF15-F4/80 co-localization in liver. GDF15 (orange), macrophages (F4/80, green), nuclei (DAPI, blue). Scale bar: 20 μm. Representative image showing focal GDF15 induction. Note that the signal is localized to discrete macrophage-enriched inflammatory niches, consistent with the physiological distribution of immune cells in hepatic tissue. (G) Hepatic GDF15 accumulation after LPS challenge. β-actin served as a loading control. Note: the detected band at ~34 kDa corresponds to the glycosylated pro-form of GDF15. (Liver-wide stress adaptation response.) (H) Persistent UQCRC1 suppression in hepatocytes (validating in vivo impairment in C).(Cell-level mitochondrial dysfunction.) (I) GDF15 induction in RAW264.7 cells. β-actin: loading control. (Cell-autonomous GDF15 upregulation.).

Article Snippet: Proteins (30 μg/lane) were separated on 10% SDS-PAGE gels, transferred to PVDF membranes (Millipore, IPVH00010), and probed with the following primary antibodies: rabbit anti-mouse UQCRC1 (Proteintech, Cat. No. 21705-1-AP, 1:1000), rabbit anti-mouse GDF15 (Proteintech, Cat. No. 27455-1-AP, 1:1000), rabbit anti-mouse HIF-1α (Proteintech, Cat. No. 20960-1-AP, 1:1000), rabbit anti-mouse SMAD7 (Proteintech, Cat. No. 725840-1-AP, 1:1000), mouse anti-mouse PKM2 (Proteintech, Cat. No. 60268-1-Ig, 1:1000), rabbit anti-mouse H3 (Proteintech, Cat. No. 17168-1-AP, 1:5000) and mouse anti-mouse β-actin (Proteintech, Cat. No. 66009-1-Ig, 1:5000).

Techniques: Histopathology, Biomarker Discovery, Control, Cell Culture, In Vivo

Journal: Frontiers in Immunology

Article Title: GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury

doi: 10.3389/fimmu.2025.1712741

Figure Lengend Snippet: Hepatoprotective effects of GDF15 overexpression against LPS-induced injury via mitochondrial function restoration. (A) Robust GDF15 expression in mouse liver following rAAV8-mGdf15 delivery. β-actin: loading control.(rAAV8-mediated hepatic GDF15 overexpression. β-actin: loading control.) (B) H&E-stained liver sections: Untreated (NC), LPS-challenged (LPS), and LPS + rAAV8-mGdf15 (LPS+GDF15). Scale bar: 50 μm. (Histopathological rescue by GDF15.) (C) TUNEL assay (green) showing apoptotic cell death. DAPI (blue): nuclei. GDF15 significantly reduces apoptosis. Scale bars: 20 μm.(GDF15-mediated suppression of apoptosis. TUNEL cells (green), nuclei (DAPI, blue).) (D) Macrophage infiltration (F4/80+, green) attenuated by GDF15 overexpression. DAPI (blue): nuclei. Scale bars: 100 μm.(Inhibition of macrophage recruitment. F4/80+ cells (green), nuclei (DAPI, blue).) (E) Hepatic UQCRC1 recovery with GDF15. β-actin: loading control.(Mitochondrial complex III rescue.) (F) Serum TNF-α, IL-6, and lactate levels (n = 5). Study groups and individual replicates are identified in the figure key. ***p < 0.001. (Systemic inflammation and metabolic stress reversal.) (G) rAAV8-mGdf15 elevates GDF15 in RAW264.7. β-actin: loading control.(Macrophage-targeted GDF15 overexpression.) (H) Effective GDF15 knockdown (si-GDF15) in RAW264.7. β-actin: loading control.(GDF15 knockdown efficiency.) (I) UQCRC1 expression in RAW264.7: Loss of GDF15 (si-GDF15) exacerbates LPS-induced UQCRC1 suppression, while GDF15 restores it.(GDF15-dependent mitochondrial protection in macrophages.) (J) Inflammatory (TNF-α, IL-6) and metabolic (lactate) markers in RAW264.7 supernatant (n = 5 independent experiments). GDF15 inhibits LPS-induced release; si-GDF15 amplifies it. Study groups and individual replicates are identified in the figure key.(GDF15-modulated macrophage inflammatory output.).

Article Snippet: Proteins (30 μg/lane) were separated on 10% SDS-PAGE gels, transferred to PVDF membranes (Millipore, IPVH00010), and probed with the following primary antibodies: rabbit anti-mouse UQCRC1 (Proteintech, Cat. No. 21705-1-AP, 1:1000), rabbit anti-mouse GDF15 (Proteintech, Cat. No. 27455-1-AP, 1:1000), rabbit anti-mouse HIF-1α (Proteintech, Cat. No. 20960-1-AP, 1:1000), rabbit anti-mouse SMAD7 (Proteintech, Cat. No. 725840-1-AP, 1:1000), mouse anti-mouse PKM2 (Proteintech, Cat. No. 60268-1-Ig, 1:1000), rabbit anti-mouse H3 (Proteintech, Cat. No. 17168-1-AP, 1:5000) and mouse anti-mouse β-actin (Proteintech, Cat. No. 66009-1-Ig, 1:5000).

Techniques: Over Expression, Expressing, Control, Staining, TUNEL Assay, Inhibition, Knockdown

Journal: Frontiers in Immunology

Article Title: GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury

doi: 10.3389/fimmu.2025.1712741

Figure Lengend Snippet: GDF15 preserves mitochondrial homeostasis in LPS-stimulated macrophages through dual regulation of SMAD7 and PKM2 pathways. (A) HIF-1α and SMAD7 expression in RAW264.7 macrophages across conditions: Untreated, LPS, LPS with rAAV8-mGdf15 overexpression (LPS+GDF15), and LPS with GDF15 knockdown (si-GDF15). β-actin: loading control.(HIF-1α suppression and SMAD7 induction by GDF15.) (B) Cytosolic and nuclear PKM2 protein levels. Lamin B1 (nuclear) and α-tubulin (cytosolic) markers validate fractionation efficiency. Study groups and individual replicates are identified in the figure key.(PKM2 subcellular redistribution modulated by GDF15.) (C) Immunofluorescence of PKM2 (red) and nuclei (DAPI, blue). Arrows indicate nuclear PKM2 accumulation. Scale bar: 15 μm.(Nuclear PKM2 enrichment upon LPS challenge mitigated by GDF15 and exacerbated by GDF15 knockdown.).

Article Snippet: Proteins (30 μg/lane) were separated on 10% SDS-PAGE gels, transferred to PVDF membranes (Millipore, IPVH00010), and probed with the following primary antibodies: rabbit anti-mouse UQCRC1 (Proteintech, Cat. No. 21705-1-AP, 1:1000), rabbit anti-mouse GDF15 (Proteintech, Cat. No. 27455-1-AP, 1:1000), rabbit anti-mouse HIF-1α (Proteintech, Cat. No. 20960-1-AP, 1:1000), rabbit anti-mouse SMAD7 (Proteintech, Cat. No. 725840-1-AP, 1:1000), mouse anti-mouse PKM2 (Proteintech, Cat. No. 60268-1-Ig, 1:1000), rabbit anti-mouse H3 (Proteintech, Cat. No. 17168-1-AP, 1:5000) and mouse anti-mouse β-actin (Proteintech, Cat. No. 66009-1-Ig, 1:5000).

Techniques: Expressing, Over Expression, Knockdown, Control, Fractionation, Immunofluorescence

Journal: Frontiers in Immunology

Article Title: GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury

doi: 10.3389/fimmu.2025.1712741

Figure Lengend Snippet: HIF-1α and PKM2 are critical effectors of GDF15-driven mitochondrial protection and anti-inflammatory responses. (A) HIF-1α inhibition by BAY 87-2243 (5 μM, 24 h). β-actin: loading control.(Pharmacological HIF-1α blockade.) (B) PKM2 inhibition by Shikonin (2 μM, 24 h). β-actin: loading control.(PKM2 activity suppression.) (C) UQCRC1 recovery in LPS-injured macrophages treated with: GDF15 overexpression, HIF-1α inhibitor (BAY), or PKM2 inhibitor (Shikonin). β-actin: loading control.(Mitochondrial complex III rescue via HIF-1α/PKM2 inhibition mirrors GDF15 effects.) (D) Inflammatory (TNF-α, IL-6) and metabolic (lactate) markers in cell supernatant (n = 5). Study groups and individual replicates are identified in the figure key. ***p < 0.001.(HIF-1α/PKM2 targeting replicates GDF15-mediated anti-inflammatory and metabolic homeostasis.) (E) UQCRC1 expression under GDF15 loss-of-function: si-GDF15 alone vs. combined with BAY 87–2243 or Shikonin. β-actin: loading control. Study groups and individual replicates are identified in the figure key.(Mitochondrial rescue in GDF15-deficient macrophages requires HIF-1α/PKM2 inhibition.) (F) Supernatant cytokines and lactate in si-GDF15 macrophages with/without inhibitors (n = 5). ***p < 0.001. (Inflammation reversal in GDF15-knockdown macrophages depends on HIF-1α/PKM2 blockade.).

Article Snippet: Proteins (30 μg/lane) were separated on 10% SDS-PAGE gels, transferred to PVDF membranes (Millipore, IPVH00010), and probed with the following primary antibodies: rabbit anti-mouse UQCRC1 (Proteintech, Cat. No. 21705-1-AP, 1:1000), rabbit anti-mouse GDF15 (Proteintech, Cat. No. 27455-1-AP, 1:1000), rabbit anti-mouse HIF-1α (Proteintech, Cat. No. 20960-1-AP, 1:1000), rabbit anti-mouse SMAD7 (Proteintech, Cat. No. 725840-1-AP, 1:1000), mouse anti-mouse PKM2 (Proteintech, Cat. No. 60268-1-Ig, 1:1000), rabbit anti-mouse H3 (Proteintech, Cat. No. 17168-1-AP, 1:5000) and mouse anti-mouse β-actin (Proteintech, Cat. No. 66009-1-Ig, 1:5000).

Techniques: Inhibition, Control, Activity Assay, Over Expression, Expressing, Knockdown

Journal: Frontiers in Immunology

Article Title: GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury

doi: 10.3389/fimmu.2025.1712741

Figure Lengend Snippet: SMAD7 activation suppresses HIF-1α to mediate GDF15-dependent mitochondrial protection in LPS-challenged macrophages. (A) Pharmacological SMAD7 activation by Asiaticoside (20 μM, 48 h). β-actin: loading control. (B) HIF-1α expression under LPS challenge: LPS alone, LPS + AVV-GDF15, or LPS + SMAD7 activation (Asiaticoside). β-actin: loading control. (C) HIF-1α modulation across conditions: LPS, LPS + si-GDF15, LPS + Asiaticoside, or LPS + si-GDF15 + Asiaticoside. β-actin: loading control.

Article Snippet: Proteins (30 μg/lane) were separated on 10% SDS-PAGE gels, transferred to PVDF membranes (Millipore, IPVH00010), and probed with the following primary antibodies: rabbit anti-mouse UQCRC1 (Proteintech, Cat. No. 21705-1-AP, 1:1000), rabbit anti-mouse GDF15 (Proteintech, Cat. No. 27455-1-AP, 1:1000), rabbit anti-mouse HIF-1α (Proteintech, Cat. No. 20960-1-AP, 1:1000), rabbit anti-mouse SMAD7 (Proteintech, Cat. No. 725840-1-AP, 1:1000), mouse anti-mouse PKM2 (Proteintech, Cat. No. 60268-1-Ig, 1:1000), rabbit anti-mouse H3 (Proteintech, Cat. No. 17168-1-AP, 1:5000) and mouse anti-mouse β-actin (Proteintech, Cat. No. 66009-1-Ig, 1:5000).

Techniques: Activation Assay, Control, Expressing

Journal: Frontiers in Immunology

Article Title: GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury

doi: 10.3389/fimmu.2025.1712741

Figure Lengend Snippet: GDF15 correlates with clinical severity in sepsis. (A) Circulating GDF15 levels: Healthy controls (HC, n=91) vs. Sepsis patients (SP, n=119). (B–N) Correlation network of GDF15 with clinical parameters: WBC, CRP, SOFA, SAA, PCT, Glu, Lactate, PLT, SOFA, ALT, AST, TBIL, IL-6 and TNF-α (n=210). Solid lines represent linear regression fits for visual trend estimation, while r and P values are derived from Spearman’s rank correlation analysis.

Article Snippet: Proteins (30 μg/lane) were separated on 10% SDS-PAGE gels, transferred to PVDF membranes (Millipore, IPVH00010), and probed with the following primary antibodies: rabbit anti-mouse UQCRC1 (Proteintech, Cat. No. 21705-1-AP, 1:1000), rabbit anti-mouse GDF15 (Proteintech, Cat. No. 27455-1-AP, 1:1000), rabbit anti-mouse HIF-1α (Proteintech, Cat. No. 20960-1-AP, 1:1000), rabbit anti-mouse SMAD7 (Proteintech, Cat. No. 725840-1-AP, 1:1000), mouse anti-mouse PKM2 (Proteintech, Cat. No. 60268-1-Ig, 1:1000), rabbit anti-mouse H3 (Proteintech, Cat. No. 17168-1-AP, 1:5000) and mouse anti-mouse β-actin (Proteintech, Cat. No. 66009-1-Ig, 1:5000).

Techniques: Derivative Assay

Journal: Journal of Personalized Medicine

Article Title: Growth Differentiation Factor-15 as an Emerging Biomarker in Cardiology: Diagnostic and Prognostic Implications

doi: 10.3390/jpm16010016

Figure Lengend Snippet: Schematic representation of GDF-15 biosynthesis, maturation, and secretion. ( a ) GDF-15 is synthesized as pre-pro-GDF-15, consisting of a signal peptide (blue), a pro-domain (yellow), and a mature C-terminal domain (red). Removal of the signal peptide generates pro-GDF-15, which rapidly dimerizes; ( b ) In the Golgi apparatus, pro-GDF-15 dimer is cleaved by PCSK3, PCSK5, and PCSK6 at the RXXR site, producing mature GDF-15; ( c ) Mature GDF-15 homodimers are secreted through the classical secretory pathway and released into circulation, while in specific cells pro-GDF-15 dimers may remain bound to the extracellular matrix until further cleavage by MMP26 or PCSKs. GDF-15: Growth Differentiation Factor-15; PCSK: proprotein convertase subtilisin–kexin; MMP26: matrix metalloproteinase 26.

Article Snippet: Human GDF-15 ELISA Kit [ ] , Proteintech , ELISA , 300 , 1250–40,000.

Techniques: Synthesized

Journal: Journal of Personalized Medicine

Article Title: Growth Differentiation Factor-15 as an Emerging Biomarker in Cardiology: Diagnostic and Prognostic Implications

doi: 10.3390/jpm16010016

Figure Lengend Snippet: Molecular regulation of GDF-15. Inflammatory and stress-related mediators (IL-1β, TNF-α, IL-2, M-CSF) regulate GDF-15 expression by activating key transcription factors such as ATF4, CHOP, p53, EGR-1, and NF-κB, emphasizing the complex and tissue-dependent nature of this regulatory network. IL-1ß: interleukin-1ß; TNF-α: tumor necrosis factor-α, IL-2: interleukin-2; MCSF-1: macrophage colony-stimulating factor-1; EGR-1: early growth response transcription factor 1; NF-Kb: Nuclear Factor kappa B; CHOP: C/EBP homologous protein; ATF4: activating transcription factor 4; GDF-15: Growth Differentiation Factor-15.

Article Snippet: Human GDF-15 ELISA Kit [ ] , Proteintech , ELISA , 300 , 1250–40,000.

Techniques: Expressing

Journal: Journal of Personalized Medicine

Article Title: Growth Differentiation Factor-15 as an Emerging Biomarker in Cardiology: Diagnostic and Prognostic Implications

doi: 10.3390/jpm16010016

Figure Lengend Snippet: GDF-15–mediated mechanisms of cardiac protection. In cardiomyocytes, GDF-15 activates the Smad2/3 and Smad1/5/8 pathways to limit hypertrophy and apoptosis, enhances myocardial survival through the PI3K/PKB signaling cascade, and inhibits pro-apoptotic pathways involving JNK, Bad, and EGFR, thereby contributing to cardiac protection. GDF-15: Growth Differentiation Factor-15; EGFR: epidermal growth factor receptor; ERK: extracellular signal-regulated kinase; PKB: protein kinase B; NF-Kb: Nuclear Factor kappa B; JNK: c-Jun N-terminal kinase; CAS-3: Caspase-3; PI3K: phosphatidylinositol 3-kinase; BAD: Bcl-2-associated death promoter.

Article Snippet: Human GDF-15 ELISA Kit [ ] , Proteintech , ELISA , 300 , 1250–40,000.

Techniques: