{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:15:37Z","timestamp":1789874137115,"version":"4.0.1"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,11,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The neonatal heart maintains its entire regeneration capacity within days after birth. Using quantitative phosphoproteomics technology, we identified that SGK3 (serine\/threonine\u2010protein kinase 3) in the neonatal heart is highly expressed and activated after myocardial infarction. This study aimed to uncover the function and related mechanisms of SGK3 on cardiomyocyte proliferation and cardiac repair after apical resection or ischemia\/reperfusion injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">The effect of SGK3 on proliferation and oxygen glucose deprivation\/reoxygenation\u2013 induced apoptosis in isolated cardiomyocytes was evaluated using cardiomyocyte\u2010specific SGK3 overexpression or knockdown adenovirus5 vector. In vivo, gain\u2010 and loss\u2010of\u2010function experiments using cardiomyocyte\u2010specific adeno\u2010associated virus 9 were performed to determine the effect of SGK3 in cardiomyocyte proliferation and cardiac repair after apical resection or ischemia\/reperfusion injury. In vitro, overexpression of SGK3 enhanced, whereas knockdown of SGK3 decreased, the cardiomyocyte proliferation ratio. In vivo, inhibiting the expression of SGK3 shortened the time window of cardiac regeneration after apical resection in neonatal mice, and overexpression of SGK3 significantly promoted myocardial repair and cardiac function recovery after ischemia\/reperfusion injury in adult mice. Mechanistically, SGK3 promoted cardiomyocyte regeneration and myocardial repair after cardiac injury by inhibiting GSK\u20103\u03b2 (glycogen synthase kinase\u20103\u03b2) activity and upregulating \u03b2\u2010catenin expression. SGK3 also upregulated the expression of cell cycle promoting genes G1\/S\u2010specific cyclin\u2010D1, c\u2010myc (cellular\u2010myelocytomatosis viral oncogene), and cdc20 (cell division cycle 20), but downregulated the expression of cell cycle negative regulators cyclin kinase inhibitor P 21 and cyclin kinase inhibitor P 27.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Our study reveals a key role of SGK3 on cardiac repair after apical resection or ischemia\/reperfusion injury, which may reopen a novel therapeutic option for myocardial infarction.<\/jats:p>\n                  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