ArticleJCI insight2020
ERRγ suppression by Sirt6 alleviates cholestatic liver injury and fibrosis.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Hepatic SIRT6 Deficiency Accelerates Female-Specific Aging Through SULT1E1-Mediated Estrogen Depletion.International journal of molecular sciences · 2026Article
- Review
- Role of Sirtuin 6 in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Current issues in molecular biology · 2026Review
- The Non-Canonical ChREBPα Activity Suppresses the Activation of Hepatic Stellate Cells and Liver Fibrosis by Antagonizing TGF-β-E2F1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A novel clinical trial for primary sclerosing cholangitis from Asia: All regional endeavors should improve global management of primary sclerosing cholangitis: Editorial on "Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial".Clinical and molecular hepatology · 2025Article
- Hepatic SIRT6 protects against cholestatic liver disease primarilyJournal of biomedical research · 2024Article
- Epigenetic modification in liver fibrosis: Promising therapeutic direction with significant challenges ahead.Acta pharmaceutica Sinica. B · 2024Review
- LncRNA MEG3: Targeting the Molecular Mechanisms and Pathogenic causes of Metabolic Diseases.Current medicinal chemistry · 2024Review
- Sex-Dependent Differences in Cholestasis: Why Estrogen Signaling May Be a Key Pathophysiological Driver.The American journal of pathology · 2023Review
- Estradiol as the Trigger of Sirtuin-1-Dependent Cell Signaling with a Potential Utility in Anti-Aging Therapies.International journal of molecular sciences · 2023Review
- Review
- SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases.Aging and disease · 2022Review
- Large Yellow Tea Extract Ameliorates Metabolic Syndrome by Suppressing Lipogenesis through SIRT6/SREBP1 Pathway and Modulating Microbiota in Leptin Receptor Knockout Rats.Foods (Basel, Switzerland) · 2022Article
- SIRT6 controls hepatic lipogenesis by suppressing LXR, ChREBP, and SREBP1.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- Vitexin ameliorates glycochenodeoxycholate-induced hepatocyte injury through SIRT6 and JAK2/STAT3 pathways.Iranian journal of basic medical sciences · 2021Article
- PSC-MSC-Derived Exosomes Protect against Kidney FibrosisInternational journal of stem cells · 2021Article
- Review
- Emerging roles of SIRT6 in human diseases and its modulators.Medicinal research reviews · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Orphan nuclear receptor estrogen-related receptor γ (ERRγ) stimulates bile acid production; however, the role and the regulatory mechanism of ERRγ in cholestatic liver disease are largely unknown. This study identifies that Sirt6 is a deacetylase of ERRγ and suggests a potentially novel mechanism by which Sirt6 activation alleviates cholestatic liver damage and fibrosis through regulating ERRγ. We observed that hepatic expression of Sirt6 is repressed, whereas hepatic expression of ERRγ is upregulated in murine cholestasis models. Hepatocyte-specific Sirt6-KO mice were more severely injured after a bile duct ligation (BDL) than WT mice, and adenoviral reexpression of Sirt6 reversed liver damage and fibrosis as demonstrated by biochemical and histological analyses. Mechanistically, Sirt6 deacetylated ERRγ, thereby destabilizing ERRγ and inhibiting its transcriptional activity. Elimination of hepatic ERRγ using Ad-shERRγ abolished the deleterious effects of Sirt6 deficiency, whereas ERRγ overexpression aggravated cholestatic liver injury. Administration of a Sirt6 deacetylase activator prevented BDL-induced liver damage and fibrosis. In patients with cholestasis, Sirt6 expression was decreased, whereas total ERRγ and acetylated ERRγ levels were increased, confirming negative regulation of ERRγ by Sirt6. Thus, Sirt6 activation represents a potentially novel therapeutic strategy for treating cholestatic liver injury.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.