{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:56:32Z","timestamp":1791618992572,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Previous studies have reported SIRT1 was inversely modulated by miR\u201034a, However, mechanism of metformin (MFN)'s\u00a0renal podocyte protection under high glucose (HG)\u00a0conditions and the connection between miR\u201034a and SIRT1 expression in diabetic nephropathy (DN)\u00a0remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We aimed to further elucidate the role of miR\u201034a in HG\u2010treated podocytes in DN. A conditionally immortalized human podocyte cell line was cultivated in <jats:sc>d<\/jats:sc>\u2010glucose (30\u2009mM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Microarray and RT\u2010qPCR\u00a0revealed that miR\u201034a was downregulated in HG\u2010treated\u00a0podocytes. Additionally, miR\u201034a levels increased in MFN\u2010treated HG\u2010induced podocytes. CCK\u20108\u00a0assay, colony formation assay,\u00a0flow cytometry,\u00a0and Western blot\u00a0detection showed that HG treatment reduced cell viability and promoted via HG treatment, and MFN treatment reversed this phenotypic change. MiR\u201034a upregulation caused restored cell viability and suppressed cell apoptosis in HG\u2010treated podocytes, and miR\u201034a downregulation led to damaged cell survival and induced apoptosis in MFN\u2010administered and HG\u2010treated podocytes. The dual luciferase reporter assay showed that SIRT1 3\u2032\u2010UTR was a direct miR\u201034a target. Further studies demonstrated an elevation in SIRT1 levels in HG\u2010exposed podocytes, whereas MFN treatment decreased SIRT1 levels. In addition, miR\u201034a upregulation led to reduced SIRT1 expression, whereas miR\u201034a inhibition increased SIRT1 levels in cells. MFN\u2010induced miR\u201034a suppresses podocyte apoptosis under HG conditions by acting on SIRT1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study proposes a promising approach to interpret the mechanisms of action of the MFN\u2010miR\u201034a axis involved in DN.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.1053","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T11:50:37Z","timestamp":1705665037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Metformin inhibits high glucose\u2010induced apoptosis of renal podocyte through regulating miR\u201034a\/SIRT1 axis"],"prefix":"10.1002","volume":"12","author":[{"given":"Xudong","family":"Zhuang","sequence":"first","affiliation":[{"name":"Department of Dialysis Linyi Traditional Chinese Medicine Hospital  Linyi Shandong 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