ArticleBritish journal of pharmacology2018
Metformin attenuates angiotensin II-induced TGFβ1 expression by targeting hepatocyte nuclear factor-4-α.
Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
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- Impaired Cardiac AMPK (5'-Adenosine Monophosphate-Activated Protein Kinase) and CaJournal of the American Heart Association · 2024Article
- Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis: Should we consider further implications?World journal of gastroenterology · 2024Article
- AMPK Signalling Pathway: A Potential Strategy for the Treatment of Heart Failure with Chinese Medicine.Journal of inflammation research · 2023Review
- Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK-dependent mechanisms.Journal of cellular and molecular medicine · 2022Review
- Telmisartan inhibits bladder smooth muscle fibrosis in neurogenic bladder rats.Experimental and therapeutic medicine · 2022Article
- Metformin: Expanding the Scope of Application-Starting Earlier than Yesterday, Canceling Later.International journal of molecular sciences · 2022Review
- AMPK inhibits Smad3-mediated autoinduction of TGF-β1 in gastric cancer cells.Journal of cellular and molecular medicine · 2021Article
- Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms.Journal of diabetes research · 2021Review
- The Demonstration of an Aqp4/Tgf-beta 1 Pathway in Murine Astrocytes Holds Implications for Both Neuromyelitis Optica and Progressive Multiple Sclerosis.International journal of molecular sciences · 2020Article
- Metformin and Vascular Diseases: A Focused Review on Smooth Muscle Cell Function.Frontiers in pharmacology · 2020Review
- Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach.Frontiers in pharmacology · 2020Article
- Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases.World journal of gastroenterology · 2019Review
- AMPK: a therapeutic target of heart failure-not only metabolism regulation.Bioscience reports · 2019Review
- AdipoRon, an adiponectin receptor agonist, attenuates cardiac remodeling induced by pressure overload.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Spotlight on small molecules in cardiovascular diseases.British journal of pharmacology · 2018Article
- Metformin attenuates angiotensin II-induced TGFβ1 expression by targeting hepatocyte nuclear factor-4-α.British journal of pharmacology · 2018Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeMetformin, a small molecule, antihyperglycaemic agent, is a well-known activator of AMP-activated protein kinase (AMPK) and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. TGFβ1 is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects of metformin on TGFβ1 production induced by angiotensin II (AngII) and the underlying mechanisms. EXPERIMENTAL APPROACH: Wild-type and AMPKα2 KEY
resultsIn CFs, metformin inhibited AngII-induced TGFβ1 expression via AMPK activation. Analysis using bioinformatics predicted a potential hepatocyte nuclear factor 4α (HNF4α)-binding site in the promoter region of the Tgfb1 gene. Overexpressing HNF4α increased TGFβ1 expression in CFs. HNF4α siRNA attenuated AngII-induced TGFβ1 production and cardiac fibrosis in vitro and in vivo. Metformin inhibited the AngII-induced increases in HNF4α protein expression and binding to the Tgfb1 promoter in CFs. In vivo, metformin blocked the AngII-induced increase in cardiac HNF4α protein levels in wild-type mice but not in AMPKα2 CONCLUSIONS AND IMPLICATIONS: HNF4α mediates AngII-induced TGFβ1 transcription and cardiac fibrosis. Metformin inhibits AngII-induced HNF4α expression via AMPK activation, thus decreasing TGFβ1 transcription and cardiac fibrosis. These findings reveal a novel antifibrotic mechanism of action of metformin and identify HNF4α as a new potential therapeutic target for cardiac fibrosis. LINKED ARTICLES: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
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