{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:10:45Z","timestamp":1791835845712,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":311,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hainan Province","doi-asserted-by":"publisher","award":["821QN425"],"award-info":[{"award-number":["821QN425"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600239"],"award-info":[{"award-number":["81600239"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. The mitochondrial dynamics and mitochondrial biogenesis are essential for maintaining the bioenergy function of mitochondria in diabetic cardiomyopathy (DCM). Previous studies have revealed that secreted frizzled\u2010related protein 2 (SFRP2) is beneficial against apoptosis and oxidative stress. However, no research has confirmed whether SFRP2 regulates oxidative stress and apoptosis through mitochondrial function in DCM. <jats:italic>Methods<\/jats:italic>. Exposure of H9C2 cardiomyocytes in high glucose (HG) 25\u2009mM and palmitic acid (PAL) 0.2\u2009mM was used to simulate DCM <jats:italic>in vitro<\/jats:italic>. H9C2 cells with SFRP2 overexpression or SFRP2 knockdown were constructed and cultured under glucolipotoxicity or normal glucose conditions. An SD rat model of type 2 diabetes mellitus (T2DM) was generated using a high\u2010fat diet combined with a low\u2010dose STZ injection. Overexpression of SFRP2 in the rat model was generated by using an adeno\u2010associated virus approach. CCK\u20108, TUNEL assay, and DHE staining were used to detect cell viability, and MitoTracker Red CMXRos was used to detect changes in mitochondrial membrane potential. We used qRT\u2010PCR and western blot to further explore the mechanisms of SFRP2 regulating mitochondrial dynamics through the AMPK\/PGC1\u2010<jats:italic>\u03b1<\/jats:italic> pathway to improve diabetic cardiomyocyte injury. <jats:italic>Results<\/jats:italic>. Our results indicated that SFRP2 was significantly downregulated in H9C2 cells and cardiac tissues in T2DM conditions, accompanied by decreased expression of mitochondrial dysfunction. The mitochondrial membrane potential was reduced, and the cells were led to oxidative stress injury and apoptosis. Furthermore, the overexpression of SFRP2 could reverse apoptosis and promote mitochondrial function in T2DM conditions <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. We also found that silencing endogenous SFRP2 could further promote glucolipotoxicity\u2010induced mitochondrial dysfunction and apoptosis in cardiomyocytes, accompanied by downregulation of p\u2010AMPK. <jats:italic>Conclusion<\/jats:italic>. SFRP2 exerted cardioprotective effects by salvaging mitochondrial function in an AMPK\u2010PGC1\u2010<jats:italic>\u03b1-<\/jats:italic>dependent manner, which modulates mitochondrial dynamics and mitochondrial biogenesis, reducing oxidative stress and apoptosis. SFRP2 may be a promising therapeutic biomarker in DCM.<\/jats:p>","DOI":"10.1155\/2021\/9265016","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T20:20:21Z","timestamp":1636402821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic 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