{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:50:14Z","timestamp":1790855414392,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic cardiomyopathy (DCM) is one of the leading causes of heart failure in patients with diabetes mellitus, with limited effective treatments. The cardioprotective effects of sodium\u2010glucose cotransporter 2(SGLT2) inhibitors have been supported by amounts of clinical trials, which largely fills the gap. However, the underlying mechanism still needs to be further explored, especially in terms of its protection against cardiac fibrosis, a crucial pathophysiological process during the development of DCM. Besides, endothelial\u2010to\u2010mesenchymal transition (EndMT) has been reported to play a pivotal role in fibroblast multiplication and cardiac fibrosis. This study aimed to evaluate the effect of SGLT2 inhibitor dapagliflozin (DAPA) on DCM especially for cardiac fibrosis and explore the underlying mechanism. In vivo, the model of type 2 diabetic rats was built with high\u2010fat feeding and streptozotocin injection. Untreated diabetic rats showed cardiac dysfunction, increased myocardial fibrosis and EndMT, which was attenuated after treatment with DAPA and metformin. In vitro, HUVECs and primary cardiac fibroblasts were treated with DAPA and exposed to high glucose (HG). HG\u2010induced EndMT in HUVECs and collagen secretion of fibroblasts were markedly inhibited by DAPA. Up\u2010regulation of TGF\u2010\u03b2\/Smad signalling and activity inhibition of AMPK\u03b1 were also reversed by DAPA treatment. Then, AMPK\u03b1 siRNA and compound C abrogated the anti\u2010EndMT effects of DAPA in HUVECs. From above all, our study implied that DAPA can protect against DCM and myocardial fibrosis through suppressing fibroblast activation and EndMT via AMPK\u03b1\u2010mediated inhibition of TGF\u2010\u03b2\/Smad signalling.<\/jats:p>","DOI":"10.1111\/jcmm.16601","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T07:27:52Z","timestamp":1624606072000},"page":"7642-7659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":207,"title":["Dapagliflozin alleviates cardiac fibrosis through suppressing EndMT and fibroblast activation via AMPK\u03b1\/TGF\u2010\u03b2\/Smad signalling in type 2 diabetic rats"],"prefix":"10.1111","volume":"25","author":[{"given":"Jingjing","family":"Tian","sequence":"first","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences The 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Medicine Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian","family":"Liu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital Zhejiang University School of Medicine Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese 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