ArticleInternational journal of biological sciences2019
Metformin Promotes the Survival of Random-Pattern Skin Flaps by Inducing Autophagy via the AMPK-mTOR-TFEB signaling pathway.
Article in International journal of biological sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and CXCL16 in OA.Arthritis research & therapy · 2023Trial
- AKT (Ser473) suppression mediates ceritinib cardiotoxicity through autophagic flux impairment and mitochondrial injury.Acta pharmacologica Sinica · 2026Article
- [Role and mechanism of infrared thermography in early identification of necrosis risk in random-pattern flaps of mice].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026Article
- Metformin in skin diseases: the role of gut microbiota and immune response.Pharmacological reports : PR · 2026Review
- Melatonin promotes skin flap survival by inhibiting ferroptosis via activation of the Nrf2/HO-1 pathway.Burns & trauma · 2026Article
- Melatonin-engineered MSCs-exosomes deliver USP4 to stabilise ARNTL and inhibit clock rhythmic ferroptosis for enhanced flap survival.Clinical and translational medicine · 2026Article
- Alpha-ketoglutarate promotes random-pattern skin flap survival by enhancing angiogenesis via PI3K/Akt/HIF-1α signaling pathway.Cell regeneration (London, England) · 2025Article
- Topical ROCEN (nanoliposomal avocado/soybean unsaponifiables) enhances survival of random-pattern skin flaps through Akt/mTOR pathway modulation.Molecular biology reports · 2025Article
- Metformin as a Modulator of Autophagy and Hypoxia Responses in the Enhancement of Wound Healing in Diabetic Rats.Inflammation · 2025Article
- Metformin sensitizes triple-negative breast cancer to histone deacetylase inhibitors by targeting FGFR4.Journal of biomedical science · 2025Article
- Research Hotspots and Frontier Trends of Autophagy in Diabetic Cardiomyopathy From 2014 to 2024: A Bibliometric Analysis.Journal of multidisciplinary healthcare · 2025Article
- Bone marrow mesenchymal stem cells modulate miR-202-3p to suppress neuronal apoptosis following spinal cord injury through autophagy activation via the AMPK, MAPK, and PI3K/AKT/mTOR signaling pathway.Scientific reports · 2024Article
- Article
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?International journal of molecular sciences · 2024Review
- Pharmacological and cell-based treatments to increase local skin flap viability in animal models.Journal of translational medicine · 2024Review
- Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke.Current neuropharmacology · 2024Article
- Anti-PCSK9 Treatment Attenuates Liver Fibrosis via Inhibiting Hypoxia-Induced Autophagy in Hepatocytes.Inflammation · 2023Article
- Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice.Signal transduction and targeted therapy · 2022Article
- Protection by metformin against severe Covid-19: An in-depth mechanistic analysis.Diabetes & metabolism · 2022Review
- Metformin promotes microglial cells to facilitate myelin debris clearance and accelerate nerve repairment after spinal cord injury.Acta pharmacologica Sinica · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Random-pattern skin flaps are widely used to close defects in reconstructive and plastic surgeries; however, they are vulnerable to necrosis, particularly in the distal portion of the flap. Here, we examined the effects of metformin on flap survival and the mechanisms underlying these effects. Following metformin treatment, the survival area, blood flow, and number of microvessels present in skin flaps were increased on postoperative day 7, whereas tissue edema was reduced. In addition, metformin promoted angiogenesis, inhibited apoptosis, relieved oxidative stress, and increased autophagy in areas of ischemia; these effects were reversed by autophagy inhibitors 3-methyladenine (3MA) or chloroquine (CQ). Either 3MA or CQ reversed the metformin-induced increase in flap viability. Moreover, metformin also activated the AMPK-mTOR-TFEB signaling pathway in ischemic areas. Inhibitions of AMPK via Compound C (CC) or AMPK shRNA adeno-associated virus (AAV) vector resulted in the downregulation of the AMPK-mTOR-TFEB signaling pathway and autophagy level in metformin-treated flaps. Taken together, our findings suggest that metformin improves the survival of random-pattern skin flaps by enhancing angiogenesis and suppressing apoptosis and oxidative stress. These effects result from increased autophagy mediated by activation of the AMPK-mTOR-TFEB signaling pathway.
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Registered trials
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 Socratic graph.