{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:45:55Z","timestamp":1778816755769,"version":"3.51.4"},"reference-count":47,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:p> Activation of NFAT (nuclear factor of activated T cells)-mediated hypertrophic signaling is a major regulatory response to hypertrophic stimuli. A recent study unveiled potential regulatory roles for microRNA-133a (miR-133a) in cardiac hypertrophy. To date, however, no connection has been made between miR-133a and NFAT signaling. In this study, we determined that NFATc4, a hypertrophy-associated mediator, is negatively regulated by miR-133a. Two conserved base-pairing sites between the NFATc4 3\u2032-untranslated region (UTR) and miR-133a were verified. Mutation of these sites in the NFATc4 3\u2032-UTR completely blocked the negative effect of miR-133a on NFATc4, suggesting that NFATc4 is a direct target for miR-133a regulation. Using a gain-of-function approach, we demonstrate that miR-133 significantly reduces the endogenous level of, as well as the hypertrophic stimulus-mediated increase in, NFATc4 gene expression. This latter effect of miR-133a on NFATc4 gene expression was coincided with an attenuated cardiomyocyte hypertrophy induced by an \u03b1-adrenergic receptor agonist. Conversely, cells treated with miR-133a inhibitor resulted in an increase in NFATc4 expression level. Application of miR-133a had no apparent effect on NFATc4 nuclear localization. We conclude that the negative regulation of NFATc4 expression contributes to miR-133a-mediated hypertrophic repression. <\/jats:p>","DOI":"10.1152\/ajpheart.00592.2009","type":"journal-article","created":{"date-parts":[[2010,2,20]],"date-time":"2010-02-20T02:42:20Z","timestamp":1266633740000},"page":"H1340-H1347","source":"Crossref","is-referenced-by-count":83,"title":["NFATc4 is negatively regulated in miR-133a-mediated cardiomyocyte hypertrophic repression"],"prefix":"10.1152","volume":"298","author":[{"given":"Qi","family":"Li","sequence":"first","affiliation":[{"name":"Hainan Provincial Key Laboratory of Tropical Medicine, Cardiovascular Disease and Research Institute, Hainan Medical College, and"},{"name":"Center for Molecular Development and Disease, Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Houston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Lin","sequence":"additional","affiliation":[{"name":"Center for Molecular Development and Disease, Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Houston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangsheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Molecular Development and Disease, Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Houston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Hainan Medical College, Haikou, Hainan, People's Republic of China; 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