{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:05:52Z","timestamp":1791378352516,"version":"4.3.2"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Cardiac hypertrophy, a maladaptive response to chronic stress, progresses to heart failure through mechanisms requiring deeper exploration. While forkhead helix transcription factor P3 (FoxP3) is well\u2010known as a key regulator in CD4<jats:sup>+<\/jats:sup> T cells, its role in cardiomyocytes remains unclear. Here, by using isoproterenol (ISO)\u2010induced cardiac hypertrophy models (40\u2009mg\/kg daily for in vivo study and 10\u2009\u03bcmol\/L for in vitro study), we revealed the protective role of FoxP3 in cardiac hypertrophy. Though modulating FoxP3 expression using siRNA or plasmid in cardiomyocytes, we found that FoxP3 knockdown exacerbated ISO\u2010induced hypertrophic responses, while overexpression of FoxP3 attenuated hypertrophic effects. The protective function of cardiomyocytic FoxP3 in vivo was further confirmed by infection of adeno\u2010associated virus. Mechanically, the cardiomyocytic FoxP3 decreased the expression of nuclear factor of activated T cells c3 (NFATc3), a key regulator of hypertrophy\u2010related genes, to suppress hypertrophy\u2010related genes, including atrial natriuretic peptide, brain natriuretic peptide and \u03b2\u2010myosin heavy chain (\u03b2\u2010MHC), and thus ameliorate hypertrophic responses. Besides, the immunoprecipitation and immunofluorescence determination showed that FoxP3 could interact with NFATc3 in the nucleus to form a transcription complex, thereby regulating the transcription activity of NFATc3. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSAs) revealed the specific binding sequences of FoxP3 in the \u03b2\u2010MHC promoter region, with binding occupancy reduced by ISO, suggesting that FoxP3 could interact with NFATc3 to down\u2010regulate the \u03b2\u2010MHC expression. Importantly, we identified triptolide (TP), a bioactive natural product, as a potent inducer of FoxP3 expression. Both in vivo (10\u2009\u03bcg\/kg daily) and in vitro (10\u2009\u03bcmol\/L) studies demonstrated that TP significantly reversed cardiac hypertrophy by upregulating FoxP3 expression, thereby inhibiting NFATc3\u2010mediated \u03b2\u2010MHC transcription. These findings highlight cardiomyocytic FoxP3 as a novel protective factor, elucidating its underlying mechanisms and demonstrating the therapeutic potential of TP in this process.<\/jats:p>","DOI":"10.1002\/jcp.70026","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T16:22:02Z","timestamp":1742833322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cardiomyocytic FoxP3 Attenuates Expression of \u03b2 Isoform of Myosin Heavy Chain During Cardiac Hypertrophy and Effects of Triptolide"],"prefix":"10.1002","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1336-7130","authenticated-orcid":false,"given":"Jia\u2010Hui","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy Army Medical University (Third Military Medical University) Chongqing 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