ArticleFrontiers in cell and developmental biology2021
Metformin Attenuates Renal Fibrosis in a Mouse Model of Adenine-Induced Renal Injury Through Inhibiting TGF-β1 Signaling Pathways.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 59 citations in OpenAlex.
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
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- Efficacy and safety of metformin versus empagliflozin on chronic kidney disease progression (MET-EMPA-CKD): a randomized controlled trial.Diabetology & metabolic syndrome · 2025Article
- 5-Hydroxytryptamine 1F receptor loss reduces renal vasculature and prevents lasmiditan-induced recovery following moderate-severe acute kidney injury in mice.American journal of physiology. Renal physiology · 2025Article
- Alterations to peritubular capillary structure in a rat model of kidney interstitial fibrosis: Implications for oxygen diffusion.Anatomical record (Hoboken, N.J. : 2007) · 2025Article
- Lasmiditan induces mitochondrial biogenesis in primary mouse renal peritubular endothelial cells and augments wound healing and tubular network formation.American journal of physiology. Cell physiology · 2025Article
- Repurposing mitochondria-targeted therapeutics for kidney diseases.Kidney international · 2025Review
- Changes in Urinary NGAL, FN, and LN Excretion in Type 2 Diabetic Patients Following Anti-Diabetic Therapy with Metformin.Journal of clinical medicine · 2025Article
- Jian-Pi-Yi-Shen formula improves kidney function by regulating gut microbiome in rats with chronic kidney disease.Frontiers in cellular and infection microbiology · 2025Article
- Article
- Adenine-induced animal model of chronic kidney disease: current applications and future perspectives.Renal failure · 2024Review
- Epithelial-mesenchymal transition in tissue repair and degeneration.Nature reviews. Molecular cell biology · 2024Review
- Potentials of Natural Antioxidants in Reducing Inflammation and Oxidative Stress in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Kidney Aging and Chronic Kidney Disease.International journal of molecular sciences · 2024Review
- Exercise alleviates renal interstitial fibrosis by ameliorating the Sirt1-mediated TGF-β1/Smad3 pathway in T2DM mice.Endocrine connections · 2024Article
- Renoprotective Effect ofPharmaceuticals (Basel, Switzerland) · 2023Article
- Metformin Alleviates Delayed Hydrocephalus after Intraventricular Hemorrhage by Inhibiting Inflammation and Fibrosis.Translational stroke research · 2023Article
- Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals.eLife · 2023Article
- Article
- Dapagliflozin alleviates renal fibrosis in a mouse model of adenine-induced renal injury by inhibiting TGF-β1/MAPK mediated mitochondrial damage.Frontiers in pharmacology · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well-known that all progressive chronic kidney disease (CKD) is pathologically characterized by tubulointerstitial fibrosis process. Multiple studies have shown the critical role of inflammation and fibrosis in the development of CKD. Hence strategies that target inflammatory and fibrotic signaling pathways may provide promising opportunities to protect against renal fibrosis. Metformin has been used as the first-line glucose-lowering agent to treat patients with type 2 diabetes mellitus (T2DM) for over 50 years. Accumulating evidence suggests the potential for additional therapeutic applications of metformin, including mitigation of renal fibrosis. In this study, the anti-fibrotic effects of metformin independent of its glucose-lowering mechanism were examined in an adenine -induced mouse model of CKD. Expressions of inflammatory markers MCP-1, F4/80 and ICAM, fibrotic markers type IV collagen and fibronectin, and the cytokine TGF-β1 were increased in adenine-induced CKD when compared to control groups and significantly attenuated by metformin treatment. Moreover, treatment with metformin inhibited the phosphorylation of Smad3, ERK1/2, and P38 and was associated with activation of the AMP-activated protein kinase (AMPK) in the kidneys of adenine-treated mice. These results indicate that metformin attenuates adenine-induced renal fibrosis through inhibition of TGF-β1 signaling pathways and activation of AMPK, independent of its glucose-lowering action.
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