ArticlePloS one2016
Wnt Pathway Stabilizes MeCP2 Protein to Repress PPAR-γ in Activation of Hepatic Stellate Cells.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
- Hepatic stellate cell-specific miR-214 expression alleviates liver fibrosis without boosting steatosis and inflammation.Journal of translational medicine · 2025Article
- Pharmacological manipulation of liver fibrosis progression using novel HDAC6 inhibitors.The FEBS journal · 2025Article
- A Computational Approach to Identify Novel Protein Targets Uncovers New Potential Mechanisms of Action of Mirtazapine S(+) and R(-) Enantiomers in Rett Syndrome.Journal of neurochemistry · 2025Article
- Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases.Diabetes & metabolism journal · 2025Review
- Downregulation of S100 calcium-binding A4 (S100A4) ameliorates hepatic fibrosisEuropean journal of histochemistry : EJH · 2025Article
- Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The interactive role of microRNA and other non-coding RNA in hepatitis B (HBV) associated fibrogenesis.Functional & integrative genomics · 2025Review
- Wnt/β-Catenin Signaling in Liver Pathobiology.Annual review of pathology · 2025Review
- Mechanobiology of portal hypertension.JHEP reports : innovation in hepatology · 2023Review
- Methyl-CpG-binding protein 2 promotes osteogenic differentiation of bone marrow mesenchymal stem cells through regulating forkhead box F1/Wnt/β-Catenin axis.Bioengineered · 2022Article
- MicroRNA-503 Targets Mothers Against Decapentaplegic Homolog 7 Enhancing Hepatic Stellate Cell Activation and Hepatic Fibrosis.Digestive diseases and sciences · 2021Article
- Wnt/β-Catenin-Dependent Transcription in Autism Spectrum Disorders.Frontiers in molecular neuroscience · 2021Review
- [Research progress of signaling pathways in liver fibrosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2019Review
- Rosiglitazone Inhibits Activation of Hepatic Stellate Cells via Up-Regulating Micro-RNA-124-3p to Alleviate Hepatic Fibrosis.Digestive diseases and sciences · 2019Article
- Wnt-β-catenin signalling in liver development, health and disease.Nature reviews. Gastroenterology & hepatology · 2019Review
- Role of Metabolism in Hepatic Stellate Cell Activation and Fibrogenesis.Frontiers in cell and developmental biology · 2018Article
- DNA methylation regulated gene expression in organ fibrosis.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Mechanisms of hepatic stellate cell activation.Nature reviews. Gastroenterology & hepatology · 2017Review
- Role of glycogen synthase kinase-3β and PPAR-γ on epithelial-to-mesenchymal transition in DSS-induced colorectal fibrosis.PloS one · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
PPAR-γ is essential for differentiation of hepatic stellate cells (HSC), and its loss due to epigenetic repression by methyl-CpG binding protein 2 (MeCP2) causes HSC myofibroblastic activation mediated in part via Wnt pathway, the key cellular event in liver fibrosis. Decreased miR-132 was previously proposed to promote MeCP2 protein translation for Ppar-γ repression in activated HSC (aHSC). The present study aimed to test this notion and to better understand the mechanisms of MeCP2 upregulation in aHSC. MeCP2 protein is increased on day 3 to 7 as HSC become activated in primary culture on plastic, but this is accompanied by increased but not reduced miR-132 or miR-212 which is also expected to target MeCP2 due to its similar sequence with miR-132. The levels of these mRNAs are decreased 40~50% in aHSCs isolated from experimental cholestatic liver fibrosis but increased 6-8 fold in aHSC from hepatotoxic liver fibrosis in rats. Suppression of either or both of miR132 and miR212 with specific anti-miRNA oligonucleotides (anti-oligo), does not affect MeCP2 protein levels in aHSCs. The Wnt antagonist FJ9 which inhibits HSC activation, increases miR-132/miR-212, reduces MeCP2 and its enrichment at 5' Ppar-γ promoter, and restores Ppar-γ expression but the anti-oligo do not prevent Ppar-γ upregulation. The pan-NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI) also reduces both MeCP2 and stabilized non-(S33/S37/Thr41)-phospho β-catenin and reverts aHSC to quiescent cells but do not affect miR-132/miR-212 levels. Wnt antagonism with FJ9 increases MeCP2 protein degradation in cultured HSC, and FJ9-mediated loss of MeCP2 is rescued by leupeptin but not by proteasome and lysozome inhibitors. In conclusion, canonical Wnt pathway increases MeCP2 protein due to protein stability which in turn represses Ppar-γ and activates HSC.
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