{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T09:12:58Z","timestamp":1775985178684,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T00:00:00Z","timestamp":1570492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiac fibrosis is a major cause of cardiac dysfunction in hypertrophic hearts. Differentiated embryonic chondrocyte gene 1 (Dec1), a basic helix\u2013loop\u2013helix transcription factor, has circadian expression in the heart; however, its role in cardiac diseases remains unknown. Therefore, using Dec1 knock-out (Dec1KO) and wild-type (WT) mice, we evaluated cardiac function and morphology at one and four weeks after transverse aortic constriction (TAC) or sham surgery. We found that Dec1KO mice retained cardiac function until four weeks after TAC. Dec1KO mice also revealed more severely hypertrophic hearts than WT mice at four weeks after TAC, whereas no significant change was observed at one week. An increase in Dec1 expression was found in myocardial and stromal cells of TAC-treated WT mice. In addition, Dec1 circadian expression was disrupted in the heart of TAC-treated WT mice. Cardiac perivascular fibrosis was suppressed in TAC-treated Dec1KO mice, with positive immunostaining of S100 calcium binding protein A4 (S100A4), alpha smooth muscle actin (\u03b1SMA), transforming growth factor beta 1 (TGF\u03b21), phosphorylation of Smad family member 3 (pSmad3), tumor necrosis factor alpha (TNF\u03b1), and cyclin-interacting protein 1 (p21). Furthermore, Dec1 expression was increased in myocardial hypertrophy and myocardial infarction of autopsy cases. Taken together, our results indicate that Dec1 deficiency suppresses cardiac fibrosis, preserving cardiac function in hypertrophic hearts. We suggest that Dec1 could be a new therapeutic target in cardiac fibrosis.<\/jats:p>","DOI":"10.3390\/ijms20194967","type":"journal-article","created":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T03:14:33Z","timestamp":1570590873000},"page":"4967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dec1 Deficiency Suppresses Cardiac Perivascular Fibrosis Induced by Transverse Aortic Constriction"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0971-4865","authenticated-orcid":false,"given":"Hue Thi","family":"Le","sequence":"first","affiliation":[{"name":"Department of Physiology, Wakayama Medical University, Wakayama 641-8509, Japan"},{"name":"Department of Physiology, Hanoi Medical University, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4435-2118","authenticated-orcid":false,"given":"Fuyuki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pathology, Wakayama Medical University, Wakayama 641-8509, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Kohsaka","sequence":"additional","affiliation":[{"name":"Department of Physiology, Wakayama Medical University, Wakayama 641-8509, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ujjal K.","family":"Bhawal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Matsudo 271-8587, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Nakao","sequence":"additional","affiliation":[{"name":"Department of Physiology, Wakayama Medical University, Wakayama 641-8509, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuteru","family":"Muragaki","sequence":"additional","affiliation":[{"name":"Department of Pathology, Wakayama Medical University, Wakayama 641-8509, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Nakata","sequence":"additional","affiliation":[{"name":"Department of Physiology, Wakayama Medical University, Wakayama 641-8509, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1161\/01.HYP.0000118584.33350.7d","article-title":"Hypertensive myocardial fibrosis and diastolic dysfunction: Another model of inflammation","volume":"43","author":"Kuwahara","year":"2004","journal-title":"Hypertension"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1161\/CIRCULATIONAHA.118.034621","article-title":"Inflammation and NLRP3 inflammasome activation initiated in response to pressure overload by Ca2+\/Calmodulin-dependent protein Kinase II \u03b4 signaling in cardiomyocytes are essential for adverse cardiac remodeling","volume":"138","author":"Suetomi","year":"2018","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1161\/HYPERTENSIONAHA.118.10845","article-title":"Hypoxia-induced mitogenic factor promotes cardiac hypertrophy via calcium-dependent and hypoxia-inducible factor-1\u03b1 mechanisms","volume":"72","author":"Kumar","year":"2018","journal-title":"Hypertension"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/nature05602","article-title":"p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload","volume":"446","author":"Sano","year":"2007","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00418-008-0541-5","article-title":"Characterization of Inflammatory and fibrotic response in a mousse model of cardiac pressure overload","volume":"131","author":"Ying","year":"2009","journal-title":"Histochem. 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