pgc-1α ko mice Search Results


pgc 1α ko mice  (Jackson Laboratory)
86
Jackson Laboratory pgc 1α ko mice
Pgc 1α Ko Mice, supplied by Jackson Laboratory, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/pgc-1%CE%B1+ko+mice/1100mjb+6+c57bl+j+tcratcrb+tg/10__1158_slash_0008___5472__can___25___1246-232-2-9
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crispr cas9 pgc 1α ko  (Santa Cruz Biotechnology)
92
Santa Cruz Biotechnology crispr cas9 pgc 1α ko
Crispr Cas9 Pgc 1α Ko, supplied by Santa Cruz Biotechnology, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/pgc-1%CE%B1+ko+mice/PGC-1%CE%B1+CRISPR%2FCas9+KO+Plasmid/pmc11372114-98-30-39
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crispr cas9 limd1 knockout ko  (Santa Cruz Biotechnology)
92
Santa Cruz Biotechnology crispr cas9 limd1 knockout ko
Fig. 4 Macrophage Foxo1 deficiency increases YAP/NICD activity and inhibits STING activation in HFD-induced oxidative stress. a Nuclear YAP and NICD expression were substantially increased in macrophages after HFD feeding. The data are representative of three experiments. b Liver macrophages were isolated from WT mice and stimulated with a mixture of 0.2 mM palmitic acid (PA) and 0.4 mM oleic acid (OA) for 24 h. PA/OA stimulation activated JNK and increased nuclear Foxo1 and PGC-1α expression in macrophages. c PA and OA stimulation increased the expression of p-LATS1 and <t>LIMD1,</t> leading to reduced cytoplasmic YAP phosphorylation and increased nuclear YAP expression in macrophages. d Immunofluorescence staining showing macrophage LIMD1 (green) and LATS1 (red) colocalization in PA/OA-stimulated macrophages. DAPI was used to visualize nuclei (blue). Scale bars, 30 μm. e Immunoprecipitation analysis showed that PA/OA challenge augmented the colocalization and interaction of LIMD1 and LATS1 in macrophages. f Liver macrophages from WT mice were transfected with <t>CRISPR/Cas9-mediated</t> LIMD1 KO or control vector after PA/OA challenge. Moreover, LIMD1 KO increased cytoplasmic YAP phosphorylation and reduced nuclear YAP expression. g Disruption of macrophage Foxo1 markedly increased PGC-1α, YAP, and NICD levels and reduced p-STING expression in response to PA/OA challenge. h Liver macrophages from Foxo1M-KO mice were transfected with CRISPR/Cas9-mediated PGC-1α KO or control vector after PA/OA stimulation. Immunoprecipitation analysis revealed that CRISPR/Cas9-mediated PGC-1α KO in the Foxo1M-KO cells reduced the interaction of YAP with the NICD and augmented p-STING expression. Notes: Foxo1M-KO activates YAP/NICD and inhibits STING activation in PA/OA-stimulated macrophages. All Western blots represent three experiments, and the data are presented as the mean±SD.
Crispr Cas9 Limd1 Knockout Ko, supplied by Santa Cruz Biotechnology, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/pgc-1%CE%B1+ko+mice/Limd1+CRISPR%2FCas9+KO+Plasmid/pm39122845-107-22-34
Average 92 stars, based on 1 article reviews
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c57bl 6j wt mice  (Jackson Laboratory)
86
Jackson Laboratory c57bl 6j wt mice
Fig. 4 Macrophage Foxo1 deficiency increases YAP/NICD activity and inhibits STING activation in HFD-induced oxidative stress. a Nuclear YAP and NICD expression were substantially increased in macrophages after HFD feeding. The data are representative of three experiments. b Liver macrophages were isolated from WT mice and stimulated with a mixture of 0.2 mM palmitic acid (PA) and 0.4 mM oleic acid (OA) for 24 h. PA/OA stimulation activated JNK and increased nuclear Foxo1 and PGC-1α expression in macrophages. c PA and OA stimulation increased the expression of p-LATS1 and <t>LIMD1,</t> leading to reduced cytoplasmic YAP phosphorylation and increased nuclear YAP expression in macrophages. d Immunofluorescence staining showing macrophage LIMD1 (green) and LATS1 (red) colocalization in PA/OA-stimulated macrophages. DAPI was used to visualize nuclei (blue). Scale bars, 30 μm. e Immunoprecipitation analysis showed that PA/OA challenge augmented the colocalization and interaction of LIMD1 and LATS1 in macrophages. f Liver macrophages from WT mice were transfected with <t>CRISPR/Cas9-mediated</t> LIMD1 KO or control vector after PA/OA challenge. Moreover, LIMD1 KO increased cytoplasmic YAP phosphorylation and reduced nuclear YAP expression. g Disruption of macrophage Foxo1 markedly increased PGC-1α, YAP, and NICD levels and reduced p-STING expression in response to PA/OA challenge. h Liver macrophages from Foxo1M-KO mice were transfected with CRISPR/Cas9-mediated PGC-1α KO or control vector after PA/OA stimulation. Immunoprecipitation analysis revealed that CRISPR/Cas9-mediated PGC-1α KO in the Foxo1M-KO cells reduced the interaction of YAP with the NICD and augmented p-STING expression. Notes: Foxo1M-KO activates YAP/NICD and inhibits STING activation in PA/OA-stimulated macrophages. All Western blots represent three experiments, and the data are presented as the mean±SD.
C57bl 6j Wt Mice, supplied by Jackson Laboratory, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/pgc-1%CE%B1+ko+mice/mice+wt/pm42100877-251-0-6
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mouse anti sqstm1 p62  (ABclonal Biotechnology)
98
ABclonal Biotechnology mouse anti sqstm1 p62
Fig. 4 Macrophage Foxo1 deficiency increases YAP/NICD activity and inhibits STING activation in HFD-induced oxidative stress. a Nuclear YAP and NICD expression were substantially increased in macrophages after HFD feeding. The data are representative of three experiments. b Liver macrophages were isolated from WT mice and stimulated with a mixture of 0.2 mM palmitic acid (PA) and 0.4 mM oleic acid (OA) for 24 h. PA/OA stimulation activated JNK and increased nuclear Foxo1 and PGC-1α expression in macrophages. c PA and OA stimulation increased the expression of p-LATS1 and <t>LIMD1,</t> leading to reduced cytoplasmic YAP phosphorylation and increased nuclear YAP expression in macrophages. d Immunofluorescence staining showing macrophage LIMD1 (green) and LATS1 (red) colocalization in PA/OA-stimulated macrophages. DAPI was used to visualize nuclei (blue). Scale bars, 30 μm. e Immunoprecipitation analysis showed that PA/OA challenge augmented the colocalization and interaction of LIMD1 and LATS1 in macrophages. f Liver macrophages from WT mice were transfected with <t>CRISPR/Cas9-mediated</t> LIMD1 KO or control vector after PA/OA challenge. Moreover, LIMD1 KO increased cytoplasmic YAP phosphorylation and reduced nuclear YAP expression. g Disruption of macrophage Foxo1 markedly increased PGC-1α, YAP, and NICD levels and reduced p-STING expression in response to PA/OA challenge. h Liver macrophages from Foxo1M-KO mice were transfected with CRISPR/Cas9-mediated PGC-1α KO or control vector after PA/OA stimulation. Immunoprecipitation analysis revealed that CRISPR/Cas9-mediated PGC-1α KO in the Foxo1M-KO cells reduced the interaction of YAP with the NICD and augmented p-STING expression. Notes: Foxo1M-KO activates YAP/NICD and inhibits STING activation in PA/OA-stimulated macrophages. All Western blots represent three experiments, and the data are presented as the mean±SD.
Mouse Anti Sqstm1 P62, supplied by ABclonal Biotechnology, used in various techniques. Bioz Stars score: 98/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/pgc-1%CE%B1+ko+mice/%5BKO+Validated%5D+SQSTM1+%2F+p62+Rabbit+mAb/10__36721_slash_pjps__2026__39__11__307__1-114-126-130
Average 98 stars, based on 1 article reviews
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rat anti-mouse lamp-1 (lysosomal-associated membrane protein 1; 553792)  (Becton Dickinson)
90
Becton Dickinson rat anti-mouse lamp-1 (lysosomal-associated membrane protein 1; 553792)
Fig. 4 Macrophage Foxo1 deficiency increases YAP/NICD activity and inhibits STING activation in HFD-induced oxidative stress. a Nuclear YAP and NICD expression were substantially increased in macrophages after HFD feeding. The data are representative of three experiments. b Liver macrophages were isolated from WT mice and stimulated with a mixture of 0.2 mM palmitic acid (PA) and 0.4 mM oleic acid (OA) for 24 h. PA/OA stimulation activated JNK and increased nuclear Foxo1 and PGC-1α expression in macrophages. c PA and OA stimulation increased the expression of p-LATS1 and <t>LIMD1,</t> leading to reduced cytoplasmic YAP phosphorylation and increased nuclear YAP expression in macrophages. d Immunofluorescence staining showing macrophage LIMD1 (green) and LATS1 (red) colocalization in PA/OA-stimulated macrophages. DAPI was used to visualize nuclei (blue). Scale bars, 30 μm. e Immunoprecipitation analysis showed that PA/OA challenge augmented the colocalization and interaction of LIMD1 and LATS1 in macrophages. f Liver macrophages from WT mice were transfected with <t>CRISPR/Cas9-mediated</t> LIMD1 KO or control vector after PA/OA challenge. Moreover, LIMD1 KO increased cytoplasmic YAP phosphorylation and reduced nuclear YAP expression. g Disruption of macrophage Foxo1 markedly increased PGC-1α, YAP, and NICD levels and reduced p-STING expression in response to PA/OA challenge. h Liver macrophages from Foxo1M-KO mice were transfected with CRISPR/Cas9-mediated PGC-1α KO or control vector after PA/OA stimulation. Immunoprecipitation analysis revealed that CRISPR/Cas9-mediated PGC-1α KO in the Foxo1M-KO cells reduced the interaction of YAP with the NICD and augmented p-STING expression. Notes: Foxo1M-KO activates YAP/NICD and inhibits STING activation in PA/OA-stimulated macrophages. All Western blots represent three experiments, and the data are presented as the mean±SD.
Rat Anti Mouse Lamp 1 (Lysosomal Associated Membrane Protein 1; 553792), supplied by Becton Dickinson, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/pgc-1%CE%B1+ko+mice/anti+lamp1/pmc05331267__EMMM___9___353___s001-7-147-159
Average 90 stars, based on 1 article reviews
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gait analysis treadmill exer gait  (Columbus Instruments)
96
Columbus Instruments gait analysis treadmill exer gait
Fig. 4 Macrophage Foxo1 deficiency increases YAP/NICD activity and inhibits STING activation in HFD-induced oxidative stress. a Nuclear YAP and NICD expression were substantially increased in macrophages after HFD feeding. The data are representative of three experiments. b Liver macrophages were isolated from WT mice and stimulated with a mixture of 0.2 mM palmitic acid (PA) and 0.4 mM oleic acid (OA) for 24 h. PA/OA stimulation activated JNK and increased nuclear Foxo1 and PGC-1α expression in macrophages. c PA and OA stimulation increased the expression of p-LATS1 and <t>LIMD1,</t> leading to reduced cytoplasmic YAP phosphorylation and increased nuclear YAP expression in macrophages. d Immunofluorescence staining showing macrophage LIMD1 (green) and LATS1 (red) colocalization in PA/OA-stimulated macrophages. DAPI was used to visualize nuclei (blue). Scale bars, 30 μm. e Immunoprecipitation analysis showed that PA/OA challenge augmented the colocalization and interaction of LIMD1 and LATS1 in macrophages. f Liver macrophages from WT mice were transfected with <t>CRISPR/Cas9-mediated</t> LIMD1 KO or control vector after PA/OA challenge. Moreover, LIMD1 KO increased cytoplasmic YAP phosphorylation and reduced nuclear YAP expression. g Disruption of macrophage Foxo1 markedly increased PGC-1α, YAP, and NICD levels and reduced p-STING expression in response to PA/OA challenge. h Liver macrophages from Foxo1M-KO mice were transfected with CRISPR/Cas9-mediated PGC-1α KO or control vector after PA/OA stimulation. Immunoprecipitation analysis revealed that CRISPR/Cas9-mediated PGC-1α KO in the Foxo1M-KO cells reduced the interaction of YAP with the NICD and augmented p-STING expression. Notes: Foxo1M-KO activates YAP/NICD and inhibits STING activation in PA/OA-stimulated macrophages. All Western blots represent three experiments, and the data are presented as the mean±SD.
Gait Analysis Treadmill Exer Gait, supplied by Columbus Instruments, used in various techniques. Bioz Stars score: 96/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/pgc-1%CE%B1+ko+mice/Gait+Analysis+Treadmill+Exer+Gait/custom%40gait-analysis-treadmill-exer-gait%4021352507
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447-ml/cf  (Bio-Techne corporation)
94
Bio-Techne corporation 447-ml/cf
Fig. 4 Macrophage Foxo1 deficiency increases YAP/NICD activity and inhibits STING activation in HFD-induced oxidative stress. a Nuclear YAP and NICD expression were substantially increased in macrophages after HFD feeding. The data are representative of three experiments. b Liver macrophages were isolated from WT mice and stimulated with a mixture of 0.2 mM palmitic acid (PA) and 0.4 mM oleic acid (OA) for 24 h. PA/OA stimulation activated JNK and increased nuclear Foxo1 and PGC-1α expression in macrophages. c PA and OA stimulation increased the expression of p-LATS1 and <t>LIMD1,</t> leading to reduced cytoplasmic YAP phosphorylation and increased nuclear YAP expression in macrophages. d Immunofluorescence staining showing macrophage LIMD1 (green) and LATS1 (red) colocalization in PA/OA-stimulated macrophages. DAPI was used to visualize nuclei (blue). Scale bars, 30 μm. e Immunoprecipitation analysis showed that PA/OA challenge augmented the colocalization and interaction of LIMD1 and LATS1 in macrophages. f Liver macrophages from WT mice were transfected with <t>CRISPR/Cas9-mediated</t> LIMD1 KO or control vector after PA/OA challenge. Moreover, LIMD1 KO increased cytoplasmic YAP phosphorylation and reduced nuclear YAP expression. g Disruption of macrophage Foxo1 markedly increased PGC-1α, YAP, and NICD levels and reduced p-STING expression in response to PA/OA challenge. h Liver macrophages from Foxo1M-KO mice were transfected with CRISPR/Cas9-mediated PGC-1α KO or control vector after PA/OA stimulation. Immunoprecipitation analysis revealed that CRISPR/Cas9-mediated PGC-1α KO in the Foxo1M-KO cells reduced the interaction of YAP with the NICD and augmented p-STING expression. Notes: Foxo1M-KO activates YAP/NICD and inhibits STING activation in PA/OA-stimulated macrophages. All Western blots represent three experiments, and the data are presented as the mean±SD.
447 Ml/Cf, supplied by Bio-Techne corporation, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/pgc-1%CE%B1+ko+mice/447-ml%2Fcf/bio-techne+corporation___447-ml%2Fcf
Average 94 stars, based on 1 article reviews
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Image Search Results


Fig. 4 Macrophage Foxo1 deficiency increases YAP/NICD activity and inhibits STING activation in HFD-induced oxidative stress. a Nuclear YAP and NICD expression were substantially increased in macrophages after HFD feeding. The data are representative of three experiments. b Liver macrophages were isolated from WT mice and stimulated with a mixture of 0.2 mM palmitic acid (PA) and 0.4 mM oleic acid (OA) for 24 h. PA/OA stimulation activated JNK and increased nuclear Foxo1 and PGC-1α expression in macrophages. c PA and OA stimulation increased the expression of p-LATS1 and LIMD1, leading to reduced cytoplasmic YAP phosphorylation and increased nuclear YAP expression in macrophages. d Immunofluorescence staining showing macrophage LIMD1 (green) and LATS1 (red) colocalization in PA/OA-stimulated macrophages. DAPI was used to visualize nuclei (blue). Scale bars, 30 μm. e Immunoprecipitation analysis showed that PA/OA challenge augmented the colocalization and interaction of LIMD1 and LATS1 in macrophages. f Liver macrophages from WT mice were transfected with CRISPR/Cas9-mediated LIMD1 KO or control vector after PA/OA challenge. Moreover, LIMD1 KO increased cytoplasmic YAP phosphorylation and reduced nuclear YAP expression. g Disruption of macrophage Foxo1 markedly increased PGC-1α, YAP, and NICD levels and reduced p-STING expression in response to PA/OA challenge. h Liver macrophages from Foxo1M-KO mice were transfected with CRISPR/Cas9-mediated PGC-1α KO or control vector after PA/OA stimulation. Immunoprecipitation analysis revealed that CRISPR/Cas9-mediated PGC-1α KO in the Foxo1M-KO cells reduced the interaction of YAP with the NICD and augmented p-STING expression. Notes: Foxo1M-KO activates YAP/NICD and inhibits STING activation in PA/OA-stimulated macrophages. All Western blots represent three experiments, and the data are presented as the mean±SD.

Journal: Experimental & molecular medicine

Article Title: The Foxo1-YAP-Notch1 axis reprograms STING-mediated innate immunity in NASH progression.

doi: 10.1038/s12276-024-01280-5

Figure Lengend Snippet: Fig. 4 Macrophage Foxo1 deficiency increases YAP/NICD activity and inhibits STING activation in HFD-induced oxidative stress. a Nuclear YAP and NICD expression were substantially increased in macrophages after HFD feeding. The data are representative of three experiments. b Liver macrophages were isolated from WT mice and stimulated with a mixture of 0.2 mM palmitic acid (PA) and 0.4 mM oleic acid (OA) for 24 h. PA/OA stimulation activated JNK and increased nuclear Foxo1 and PGC-1α expression in macrophages. c PA and OA stimulation increased the expression of p-LATS1 and LIMD1, leading to reduced cytoplasmic YAP phosphorylation and increased nuclear YAP expression in macrophages. d Immunofluorescence staining showing macrophage LIMD1 (green) and LATS1 (red) colocalization in PA/OA-stimulated macrophages. DAPI was used to visualize nuclei (blue). Scale bars, 30 μm. e Immunoprecipitation analysis showed that PA/OA challenge augmented the colocalization and interaction of LIMD1 and LATS1 in macrophages. f Liver macrophages from WT mice were transfected with CRISPR/Cas9-mediated LIMD1 KO or control vector after PA/OA challenge. Moreover, LIMD1 KO increased cytoplasmic YAP phosphorylation and reduced nuclear YAP expression. g Disruption of macrophage Foxo1 markedly increased PGC-1α, YAP, and NICD levels and reduced p-STING expression in response to PA/OA challenge. h Liver macrophages from Foxo1M-KO mice were transfected with CRISPR/Cas9-mediated PGC-1α KO or control vector after PA/OA stimulation. Immunoprecipitation analysis revealed that CRISPR/Cas9-mediated PGC-1α KO in the Foxo1M-KO cells reduced the interaction of YAP with the NICD and augmented p-STING expression. Notes: Foxo1M-KO activates YAP/NICD and inhibits STING activation in PA/OA-stimulated macrophages. All Western blots represent three experiments, and the data are presented as the mean±SD.

Article Snippet: BMMs (1 × 10 6 cells/well) from WT, Foxo1FL/FL, Foxo1M-KO, and Foxo1/Notch1M-DKO mice were cultured for seven days and then transfected with CRISPR/Cas9-LIMD1 knockout (KO), CRISPR/Cas9-PGC-1α KO, CRISPR/Cas9-cGAS KO, and CRISPR/Cas9-YAP-KO or control vectors (Santa Cruz Biotechnology).

Techniques: Activity Assay, Activation Assay, Expressing, Isolation, Phospho-proteomics, Staining, Immunoprecipitation, Transfection, CRISPR, Control, Plasmid Preparation, Disruption, Western Blot

Fig. 6 Disruption of macrophage Notch1 signaling activates cGAS and increases STING-mediated liver inflammation and fibrosis in HFD- induced NASH. a Foxo1/Notch1M-DKO increased cGAS, p-STING, p-TBK1, p-P65, and nuclear PGC-1α, LIMD1, and YAP expression in steatotic livers after 24 weeks of HFD feeding. b Immunofluorescence staining showed that Foxo1/Notch1M-DKO increased CD11b+ macrophage accumulation in steatotic livers (n = 6 mice/group). Quantification of CD11b+ macrophages; scale bars, 100 μm. c Foxo1/Notch1M-DKO increased TNF-α, IL-1β, IL-6, and CXCL-10 expression and decreased IL-10 levels in steatotic livers (n = 6 samples/group). d The liver/body weight ratio was significantly increased in the HFD-fed Foxo1/Notch1M-DKO mice (n = 6 samples/group). e TG and TC (mg/g) lipid levels were significantly increased in the HFD- fed Foxo1/Notch1M-DKO mice (n = 6 samples/group). f Representative histological staining (H&E and Oil Red O) showing that the livers from the HFD-fed Foxo1/Notch1M-DKO mice exhibited increased lipid accumulation (n = 6 mice/group). Scale bars, 100 μm. g NASs (NAFLD activity scores) were measured based on histological images and were significantly increased in the Foxo1/Notch1M-DKO group (n = 6 mice/group). h Serum ALT and AST levels were increased in the HFD-fed Foxo1/Notch1M-DKO mice (IU/L) (n = 6 samples/group). i Representative histological and immunohistochemical staining (Sirius Red and Masson) of steatotic liver tissues showing augmented liver fibrosis in the Foxo1/Notch1M-DKO mice (n = 6 mice/group). Scale bars, 100 μm. j Increased mRNA expression of profibrotic genes, including αSMA, Col1α1, TGF-β1, CCL2, and TIMP1, in the Foxo1/Notch1M-DKO livers after HFD feeding (n = 6 samples/group). Notes: Foxo1/Notch1M-DKO activates cGAS, increases the STING-mediated inflammatory response, and exacerbates liver fibrosis in HFD-induced NASH. All the data are presented as the mean ± SD. Statistical analysis was performed using the permutation t test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Journal: Experimental & molecular medicine

Article Title: The Foxo1-YAP-Notch1 axis reprograms STING-mediated innate immunity in NASH progression.

doi: 10.1038/s12276-024-01280-5

Figure Lengend Snippet: Fig. 6 Disruption of macrophage Notch1 signaling activates cGAS and increases STING-mediated liver inflammation and fibrosis in HFD- induced NASH. a Foxo1/Notch1M-DKO increased cGAS, p-STING, p-TBK1, p-P65, and nuclear PGC-1α, LIMD1, and YAP expression in steatotic livers after 24 weeks of HFD feeding. b Immunofluorescence staining showed that Foxo1/Notch1M-DKO increased CD11b+ macrophage accumulation in steatotic livers (n = 6 mice/group). Quantification of CD11b+ macrophages; scale bars, 100 μm. c Foxo1/Notch1M-DKO increased TNF-α, IL-1β, IL-6, and CXCL-10 expression and decreased IL-10 levels in steatotic livers (n = 6 samples/group). d The liver/body weight ratio was significantly increased in the HFD-fed Foxo1/Notch1M-DKO mice (n = 6 samples/group). e TG and TC (mg/g) lipid levels were significantly increased in the HFD- fed Foxo1/Notch1M-DKO mice (n = 6 samples/group). f Representative histological staining (H&E and Oil Red O) showing that the livers from the HFD-fed Foxo1/Notch1M-DKO mice exhibited increased lipid accumulation (n = 6 mice/group). Scale bars, 100 μm. g NASs (NAFLD activity scores) were measured based on histological images and were significantly increased in the Foxo1/Notch1M-DKO group (n = 6 mice/group). h Serum ALT and AST levels were increased in the HFD-fed Foxo1/Notch1M-DKO mice (IU/L) (n = 6 samples/group). i Representative histological and immunohistochemical staining (Sirius Red and Masson) of steatotic liver tissues showing augmented liver fibrosis in the Foxo1/Notch1M-DKO mice (n = 6 mice/group). Scale bars, 100 μm. j Increased mRNA expression of profibrotic genes, including αSMA, Col1α1, TGF-β1, CCL2, and TIMP1, in the Foxo1/Notch1M-DKO livers after HFD feeding (n = 6 samples/group). Notes: Foxo1/Notch1M-DKO activates cGAS, increases the STING-mediated inflammatory response, and exacerbates liver fibrosis in HFD-induced NASH. All the data are presented as the mean ± SD. Statistical analysis was performed using the permutation t test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Article Snippet: BMMs (1 × 10 6 cells/well) from WT, Foxo1FL/FL, Foxo1M-KO, and Foxo1/Notch1M-DKO mice were cultured for seven days and then transfected with CRISPR/Cas9-LIMD1 knockout (KO), CRISPR/Cas9-PGC-1α KO, CRISPR/Cas9-cGAS KO, and CRISPR/Cas9-YAP-KO or control vectors (Santa Cruz Biotechnology).

Techniques: Disruption, Expressing, Staining, Activity Assay, Immunohistochemical staining

Fig. 8 The Foxo1–YAP axis modulates STING-mediated liver inflammation and steatosis in HFD-induced NASH. a Representative histological staining (H&E and Oil Red O) showing that the Foxo1M-KO mice exhibited decreased lipid accumulation, whereas the Foxo1/YAPM-DKO mice exhibited increased hepatic steatosis after 24 weeks of HFD feeding (n = 6 mice/group). Scale bars, 100 μm. b The NAS (NAFLD activity score) based on histological images was measured and found to be significantly increased in the Foxo1/YAPM-DKO group (n = 6 mice/group). c The liver/ body weight ratios were significantly greater in the Foxo1/YAPM-DKO mice (n = 6 samples/group). d The TG and TC levels (mg/g) were significantly increased in the Foxo1/YAPM-DKO mice (n = 6 samples/group). e The Foxo1/YAPM-DKO mice exhibited significantly increased serum ALT and AST levels (IU/L) (n = 6 samples/group). f Representative immunofluorescence and immunohistochemistry images (α-SMA and Masson) showing significantly increased liver fibrosis in the Foxo1/YAPM-DKO livers (n = 6 mice/group). Scale bars, 100 μm. g Quantitative RT‒PCR analysis showed that Foxo1/YAPM-DKO increased cGAS, p-STING, p-TBK1, and p-P65 expression in steatotic livers (n = 6 samples/group). h Western blot analysis revealed that Foxo1/YAPM-DKO increased cGAS, p-STING, p-TBK1, and p-P65 expression and increased nuclear PGC-1α, LIMD1, and NICD expression in steatotic livers. The data are representative of three experiments. i Immunofluorescence staining showed increased CD11b+ macrophage accumulation in ischemic livers (n = 6 mice/group). Quantification of CD11b+ macrophages; scale bars, 100 μm. j The mRNA levels of TNF-α, IL-1β, IL-6, and CXCL-10 were increased, and the IL-10 level was decreased in the steatotic Foxo1/YAPM-DKO livers (n = 6 samples/group). Notes: Foxo1/ YAPM-DKO exacerbates STING-mediated liver inflammation, steatosis, and fibrosis in mice with HFD-induced NASH. All the data are presented as the mean±SD. Statistical analysis was performed using the permutation t test. *P < 0.05, **P < 0.01, ***P < 0.001.

Journal: Experimental & molecular medicine

Article Title: The Foxo1-YAP-Notch1 axis reprograms STING-mediated innate immunity in NASH progression.

doi: 10.1038/s12276-024-01280-5

Figure Lengend Snippet: Fig. 8 The Foxo1–YAP axis modulates STING-mediated liver inflammation and steatosis in HFD-induced NASH. a Representative histological staining (H&E and Oil Red O) showing that the Foxo1M-KO mice exhibited decreased lipid accumulation, whereas the Foxo1/YAPM-DKO mice exhibited increased hepatic steatosis after 24 weeks of HFD feeding (n = 6 mice/group). Scale bars, 100 μm. b The NAS (NAFLD activity score) based on histological images was measured and found to be significantly increased in the Foxo1/YAPM-DKO group (n = 6 mice/group). c The liver/ body weight ratios were significantly greater in the Foxo1/YAPM-DKO mice (n = 6 samples/group). d The TG and TC levels (mg/g) were significantly increased in the Foxo1/YAPM-DKO mice (n = 6 samples/group). e The Foxo1/YAPM-DKO mice exhibited significantly increased serum ALT and AST levels (IU/L) (n = 6 samples/group). f Representative immunofluorescence and immunohistochemistry images (α-SMA and Masson) showing significantly increased liver fibrosis in the Foxo1/YAPM-DKO livers (n = 6 mice/group). Scale bars, 100 μm. g Quantitative RT‒PCR analysis showed that Foxo1/YAPM-DKO increased cGAS, p-STING, p-TBK1, and p-P65 expression in steatotic livers (n = 6 samples/group). h Western blot analysis revealed that Foxo1/YAPM-DKO increased cGAS, p-STING, p-TBK1, and p-P65 expression and increased nuclear PGC-1α, LIMD1, and NICD expression in steatotic livers. The data are representative of three experiments. i Immunofluorescence staining showed increased CD11b+ macrophage accumulation in ischemic livers (n = 6 mice/group). Quantification of CD11b+ macrophages; scale bars, 100 μm. j The mRNA levels of TNF-α, IL-1β, IL-6, and CXCL-10 were increased, and the IL-10 level was decreased in the steatotic Foxo1/YAPM-DKO livers (n = 6 samples/group). Notes: Foxo1/ YAPM-DKO exacerbates STING-mediated liver inflammation, steatosis, and fibrosis in mice with HFD-induced NASH. All the data are presented as the mean±SD. Statistical analysis was performed using the permutation t test. *P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: BMMs (1 × 10 6 cells/well) from WT, Foxo1FL/FL, Foxo1M-KO, and Foxo1/Notch1M-DKO mice were cultured for seven days and then transfected with CRISPR/Cas9-LIMD1 knockout (KO), CRISPR/Cas9-PGC-1α KO, CRISPR/Cas9-cGAS KO, and CRISPR/Cas9-YAP-KO or control vectors (Santa Cruz Biotechnology).

Techniques: Staining, Activity Assay, Immunohistochemistry, Expressing, Western Blot