{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:08:01Z","timestamp":1791331681111,"version":"4.3.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T00:00:00Z","timestamp":1487116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T00:00:00Z","timestamp":1487116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A long non-coding RNA (lncRNA), named myocardial infarction associated transcript (MIAT), has been documented to confer risk of myocardial infarction (MI). The aim of this study is to elucidate the pathophysiological role of MIAT in regulation of cardiac fibrosis. In a mouse model of MI, we found that MIAT was remarkably up-regulated, which was accompanied by cardiac interstitial fibrosis. MIAT up-regulation in MI was accompanied by deregulation of some fibrosis-related regulators: down-regulation of miR-24 and up-regulation of Furin and TGF-\u03b21. Most notably, knockdown of endogenous MIAT by its siRNA reduced cardiac fibrosis and improved cardiac function and restored the deregulated expression of the fibrosis-related regulators. In cardiac fibroblasts treated with serum or angiotensin II, similar up-regulation of MIAT and down-regulation of miR-24 were consistently observed. These changes promoted fibroblasts proliferation and collagen accumulation, whereas knockdown of MIAT by siRNA or overexpression of miR-24 with its mimic abrogated the fibrogenesis. Our study therefore has identified MIAT as the first pro-fibrotic lncRNA in heart and unraveled the role of MIAT in the pathogenesis of MI. These findings also promise that normalization of MIAT level may prove to be a therapeutic option for the treatment of MI-induced cardiac fibrosis and the associated cardiac dysfunction.<\/jats:p>","DOI":"10.1038\/srep42657","type":"journal-article","created":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T05:32:36Z","timestamp":1487136756000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":183,"title":["MIAT Is a Pro-fibrotic Long Non-coding RNA Governing Cardiac Fibrosis in Post-infarct Myocardium"],"prefix":"10.1038","volume":"7","author":[{"given":"Xuefeng","family":"Qu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenjian","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ti","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfeng","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baofeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,15]]},"reference":[{"key":"BFsrep42657_CR1","doi-asserted-by":"publisher","first-page":"e69","DOI":"10.1161\/CIRCULATIONAHA.106.179918","volume":"115","author":"W Rosamond","year":"2007","unstructured":"Rosamond, W. et al. Heart disease and stroke statistics\u20132007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115, e69\u2013171, doi: 10.1161\/CIRCULATIONAHA.106.179918 (2007).","journal-title":"Circulation"},{"key":"BFsrep42657_CR2","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1161\/CIRCULATIONAHA.106.658948","volume":"115","author":"CS Fox","year":"2007","unstructured":"Fox, C. S. et al. Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study. Circulation 115, 1544\u20131550, doi: 10.1161\/CIRCULATIONAHA.106.658948 (2007).","journal-title":"Circulation"},{"key":"BFsrep42657_CR3","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1161\/01.res.0000046452.67724.b8","volume":"91","author":"I Manabe","year":"2002","unstructured":"Manabe, I., Shindo, T. & Nagai, R. Gene Expression in Fibroblasts and Fibrosis: Involvement in Cardiac Hypertrophy. Circulation research 91, 1103\u20131113, doi: 10.1161\/01.res.0000046452.67724.b8 (2002).","journal-title":"Circulation research"},{"key":"BFsrep42657_CR4","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1369\/jhc.4A6560.2005","volume":"53","author":"RG Dean","year":"2005","unstructured":"Dean, R. G. Connective Tissue Growth Factor and Cardiac Fibrosis after Myocardial Infarction. Journal of Histochemistry and Cytochemistry 53, 1245\u20131256, doi: 10.1369\/jhc.4A6560.2005 (2005).","journal-title":"Journal of Histochemistry and Cytochemistry"},{"key":"BFsrep42657_CR5","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1016\/S0735-1097(01)01518-2","volume":"38","author":"CM Yu","year":"2001","unstructured":"Yu, C. M., Tipoe, G. L., Wing-Hon Lai, K. & Lau, C. P. Effects of combination of angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist on inflammatory cellular infiltration and myocardial interstitial fibrosis after acute myocardial infarction. Journal of the American College of Cardiology 38, 1207\u20131215 (2001).","journal-title":"Journal of the American College of Cardiology"},{"key":"BFsrep42657_CR6","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1161\/CIRCULATIONAHA.112.094524","volume":"126","author":"Z Pan","year":"2012","unstructured":"Pan, Z. et al. MicroRNA-101 inhibited postinfarct cardiac fibrosis and improved left ventricular compliance via the FBJ osteosarcoma oncogene\/transforming growth factor-beta1 pathway. Circulation 126, 840\u2013850, doi: 10.1161\/CIRCULATIONAHA.112.094524 (2012).","journal-title":"Circulation"},{"key":"BFsrep42657_CR7","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.cardiores.2006.10.002","volume":"74","author":"M Bujak","year":"2007","unstructured":"Bujak, M. & Frangogiannis, N. G. The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovascular research 74, 184\u2013195, doi: 10.1016\/j.cardiores.2006.10.002 (2007).","journal-title":"Cardiovascular research"},{"key":"BFsrep42657_CR8","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/35043051","volume":"1","author":"J Massague","year":"2000","unstructured":"Massague, J. How cells read TGF-beta signals. Nature reviews. Molecular cell biology 1, 169\u2013178, doi: 10.1038\/35043051 (2000).","journal-title":"Nature reviews. Molecular cell biology"},{"key":"BFsrep42657_CR9","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1161\/CIRCRESAHA.108.182535","volume":"104","author":"RF Duisters","year":"2009","unstructured":"Duisters, R. F. et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circulation research 104, 170\u2013178, 176p following 178, doi: 10.1161\/CIRCRESAHA.108.182535 (2009).","journal-title":"Circulation research"},{"key":"BFsrep42657_CR10","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1161\/CIRCRESAHA.109.202176","volume":"106","author":"SJ Matkovich","year":"2010","unstructured":"Matkovich, S. J. et al. MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts. Circulation research 106, 166\u2013175, doi: 10.1161\/CIRCRESAHA.109.202176 (2010).","journal-title":"Circulation research"},{"key":"BFsrep42657_CR11","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1111\/j.1582-4934.2012.01523.x","volume":"16","author":"J Wang","year":"2012","unstructured":"Wang, J. et al. MicroRNA-24 regulates cardiac fibrosis after myocardial infarction. Journal of cellular and molecular medicine 16, 2150\u20132160, doi: 10.1111\/j.1582-4934.2012.01523.x (2012).","journal-title":"Journal of cellular and molecular medicine"},{"key":"BFsrep42657_CR12","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1051\/medsci\/2011274009","volume":"27","author":"T Derrien","year":"2011","unstructured":"Derrien, T. & Guigo, R. [Long non-coding RNAs with enhancer-like function in human cells]. Medecine sciences: M\/S 27, 359\u2013361, doi: 10.1051\/medsci\/2011274009 (2011).","journal-title":"Medecine sciences: M\/S"},{"key":"BFsrep42657_CR13","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/nature07672","volume":"458","author":"M Guttman","year":"2009","unstructured":"Guttman, M. et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458, 223\u2013227, doi: 10.1038\/nature07672 (2009).","journal-title":"Nature"},{"key":"BFsrep42657_CR14","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1016\/j.cell.2013.02.016","volume":"152","author":"JT Lee","year":"2013","unstructured":"Lee, J. T. & Bartolomei, M. S. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 152, 1308\u20131323, doi: 10.1016\/j.cell.2013.02.016 (2013).","journal-title":"Cell"},{"key":"BFsrep42657_CR15","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.cell.2011.03.014","volume":"145","author":"T Nagano","year":"2011","unstructured":"Nagano, T. & Fraser, P. No-nonsense functions for long noncoding RNAs. Cell 145, 178\u2013181, doi: 10.1016\/j.cell.2011.03.014 (2011).","journal-title":"Cell"},{"key":"BFsrep42657_CR16","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.cell.2011.09.028","volume":"147","author":"M Cesana","year":"2011","unstructured":"Cesana, M. et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147, 358\u2013369, doi: 10.1016\/j.cell.2011.09.028 (2011).","journal-title":"Cell"},{"key":"BFsrep42657_CR17","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1161\/CIRCRESAHA.114.302476","volume":"114","author":"K Wang","year":"2014","unstructured":"Wang, K. et al. The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489. Circulation research 114, 1377\u20131388, doi: 10.1161\/CIRCRESAHA.114.302476 (2014).","journal-title":"Circulation research"},{"key":"BFsrep42657_CR18","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1007\/s10038-006-0070-9","volume":"51","author":"N Ishii","year":"2006","unstructured":"Ishii, N. et al. Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. Journal of human genetics 51, 1087\u20131099, doi: 10.1007\/s10038-006-0070-9 (2006).","journal-title":"Journal of human genetics"},{"key":"BFsrep42657_CR19","doi-asserted-by":"publisher","first-page":"3596","DOI":"10.1038\/ncomms4596","volume":"5","author":"K Wang","year":"2014","unstructured":"Wang, K. et al. CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nature communications 5, 3596, doi: 10.1038\/ncomms4596 (2014).","journal-title":"Nature communications"},{"key":"BFsrep42657_CR20","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nature13596","volume":"514","author":"P Han","year":"2014","unstructured":"Han, P. et al. A long noncoding RNA protects the heart from pathological hypertrophy. Nature 514, 102\u2013106, doi: 10.1038\/nature13596 (2014).","journal-title":"Nature"},{"key":"BFsrep42657_CR21","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1161\/CIRCRESAHA.116.305510","volume":"116","author":"B Yan","year":"2015","unstructured":"Yan, B. et al. lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circulation research 116, 1143\u20131156, doi: 10.1161\/CIRCRESAHA.116.305510 (2015).","journal-title":"Circulation research"},{"key":"BFsrep42657_CR22","doi-asserted-by":"publisher","first-page":"e1000378","DOI":"10.1371\/journal.pgen.1000378","volume":"5","author":"AS Schaefer","year":"2009","unstructured":"Schaefer, A. S. et al. Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis. PLoS genetics 5, e1000378, doi: 10.1371\/journal.pgen.1000378 (2009).","journal-title":"PLoS genetics"},{"key":"BFsrep42657_CR23","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1161\/ATVBAHA.109.189522","volume":"29","author":"O Jarinova","year":"2009","unstructured":"Jarinova, O. et al. Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus. Arteriosclerosis, thrombosis, and vascular biology 29, 1671\u20131677, doi: 10.1161\/ATVBAHA.109.189522 (2009).","journal-title":"Arteriosclerosis, thrombosis, and vascular biology"},{"key":"BFsrep42657_CR24","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.1093\/hmg\/dds165","volume":"21","author":"S Smemo","year":"2012","unstructured":"Smemo, S. et al. Regulatory variation in a TBX5 enhancer leads to isolated congenital heart disease. Human molecular genetics 21, 3255\u20133263, doi: 10.1093\/hmg\/dds165 (2012).","journal-title":"Human molecular genetics"},{"key":"BFsrep42657_CR25","doi-asserted-by":"publisher","first-page":"6779","DOI":"10.1038\/ncomms7779","volume":"6","author":"K Wang","year":"2015","unstructured":"Wang, K. et al. APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p. Nature communications 6, 6779, doi: 10.1038\/ncomms7779 (2015).","journal-title":"Nature communications"},{"key":"BFsrep42657_CR26","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.cardiores.2004.03.010","volume":"63","author":"P Stawowy","year":"2004","unstructured":"Stawowy, P. et al. Regulation of matrix metalloproteinase MT1-MMP\/MMP-2 in cardiac fibroblasts by TGF-beta1 involves furin-convertase. Cardiovascular research 63, 87\u201397, doi: 10.1016\/j.cardiores.2004.03.010 (2004).","journal-title":"Cardiovascular research"},{"key":"BFsrep42657_CR27","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1093\/cvr\/cvp015","volume":"82","author":"S Roy","year":"2009","unstructured":"Roy, S. et al. MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovascular research 82, 21\u201329, doi: 10.1093\/cvr\/cvp015 (2009).","journal-title":"Cardiovascular research"},{"key":"BFsrep42657_CR28","doi-asserted-by":"publisher","first-page":"13027","DOI":"10.1073\/pnas.0805038105","volume":"105","author":"E van Rooij","year":"2008","unstructured":"van Rooij, E. et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proceedings of the National Academy of Sciences of the United States of America 105, 13027\u201313032, doi: 10.1073\/pnas.0805038105 (2008).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep42657_CR29","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1111\/jcmm.12218","volume":"18","author":"S Chen","year":"2014","unstructured":"Chen, S. et al. Cardiac miR-133a overexpression prevents early cardiac fibrosis in diabetes. J Cell Mol Med 18, 415\u2013421, doi: 10.1111\/jcmm.12218 (2014).","journal-title":"J Cell Mol Med"},{"key":"BFsrep42657_CR30","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1093\/cvr\/cvs230","volume":"96","author":"W Chu","year":"2012","unstructured":"Chu, W. et al. Arsenic-induced interstitial myocardial fibrosis reveals a new insight into drug-induced long QT syndrome. Cardiovascular research 96, 90\u201398, doi: 10.1093\/cvr\/cvs230 (2012).","journal-title":"Cardiovascular research"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep42657.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep42657","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep42657.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T20:27:30Z","timestamp":1671827250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep42657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,15]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,5,12]]}},"alternative-id":["BFsrep42657"],"URL":"https:\/\/doi.org\/10.1038\/srep42657","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727307579.793551664","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,15]]},"assertion":[{"value":"26 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"42657"}}