{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:59:54Z","timestamp":1790816394072,"version":"4.1.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2019,10,11]]},"abstract":"\n Rationale:<\/jats:title>\n \n Pathogenic variations in the lamin gene (\n LMNA<\/jats:italic>\n ) cause familial dilated cardiomyopathy (DCM).\n LMNA<\/jats:italic>\n insufficiency caused by\n LMNA<\/jats:italic>\n pathogenic variants is believed to be the basic mechanism underpinning\n LMNA<\/jats:italic>\n -related DCM.\n <\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n \n To assess whether silencing of cardiac\n Lmna<\/jats:italic>\n causes DCM and investigate the role of Yin Yang 1 (\n Yy1<\/jats:italic>\n ) in suppressing\n Lmna<\/jats:italic>\n DCM.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results:<\/jats:title>\n \n We developed a\n Lmna<\/jats:italic>\n DCM mouse model induced by cardiac-specific\n Lmna<\/jats:italic>\n short hairpin RNA. Silencing of cardiac\n Lmna<\/jats:italic>\n induced DCM with associated cardiac fibrosis and inflammation. We demonstrated that upregulation of\n Yy1<\/jats:italic>\n suppressed\n Lmna<\/jats:italic>\n DCM and cardiac fibrosis by inducing\n Bmp7<\/jats:italic>\n expression and preventing upregulation of\n Ctgf<\/jats:italic>\n . Knockdown of upregulated\n Bmp7<\/jats:italic>\n attenuated the suppressive effect of\n Yy1<\/jats:italic>\n on DCM and cardiac fibrosis. However, upregulation of\n Bmp7<\/jats:italic>\n alone was not sufficient to suppress DCM and cardiac fibrosis. Importantly, upregulation of\n Bmp7<\/jats:italic>\n together with\n Ctgf<\/jats:italic>\n silencing significantly suppressed DCM and cardiac fibrosis. Mechanistically, upregulation of\n Yy1<\/jats:italic>\n regulated\n Bmp7<\/jats:italic>\n and\n Ctgf<\/jats:italic>\n reporter activities and modulated\n Bmp7<\/jats:italic>\n and\n Ctgf<\/jats:italic>\n gene expression in cardiomyocytes. Downregulation of\n Ctgf<\/jats:italic>\n inhibited TGF-\u03b2 (transforming growth factor-\u03b2)\/Smad signaling in DCM hearts. Regulation of both\n Bmp7<\/jats:italic>\n and\n Ctgf<\/jats:italic>\n further suppressed TGF\u03b2\/Smad signaling. In addition, co-modulation of\n Bmp7<\/jats:italic>\n and\n Ctgf<\/jats:italic>\n reduced CD3+ T cell numbers in DCM hearts.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n Our findings demonstrate that upregulation of\n Yy1<\/jats:italic>\n or co-modulation of\n Bmp7<\/jats:italic>\n and\n Ctgf<\/jats:italic>\n offer novel therapeutic strategies for the treatment of DCM caused by\n LMNA<\/jats:italic>\n insufficiency.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circresaha.119.314794","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T05:00:18Z","timestamp":1568005218000},"page":"834-846","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":56,"title":["Yin Yang 1 Suppresses Dilated Cardiomyopathy and Cardiac Fibrosis Through Regulation of\n Bmp7<\/i>\n and\n Ctgf<\/i>"],"prefix":"10.1161","volume":"125","author":[{"given":"Chia Yee","family":"Tan","sequence":"first","affiliation":[{"name":"From the Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., J.J.)"},{"name":"Cardiovascular Research Institute, National University Health System, Centre for Translational Medicine, Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., M.A.-J., J.W.W., R.S.F., J.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Xuan","family":"Wong","sequence":"additional","affiliation":[{"name":"From the Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., J.J.)"},{"name":"Cardiovascular Research Institute, National University Health System, Centre for Translational Medicine, Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., M.A.-J., J.W.W., R.S.F., J.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pui Shi","family":"Chan","sequence":"additional","affiliation":[{"name":"From the Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., J.J.)"},{"name":"Cardiovascular Research Institute, National University Health System, Centre for Translational Medicine, Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., M.A.-J., J.W.W., R.S.F., J.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansen","family":"Tan","sequence":"additional","affiliation":[{"name":"From the Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., J.J.)"},{"name":"Cardiovascular Research Institute, National University Health System, Centre for Translational Medicine, Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., M.A.-J., J.W.W., R.S.F., J.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liao","sequence":"additional","affiliation":[{"name":"From the Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., J.J.)"},{"name":"Cardiovascular Research Institute, National University Health System, Centre for Translational Medicine, Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., M.A.-J., J.W.W., R.S.F., J.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., J.J.)"},{"name":"Cardiovascular Research Institute, National University Health System, Centre for Translational Medicine, Singapore (C.Y.T., J.X.W., P.S.C., H.T., D.L., W.C., M.A.-J., J.W.W., R.S.F., 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