{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:54:32Z","timestamp":1788454472833,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974295"],"award-info":[{"award-number":["81974295"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>\n                    Myocardial infarction or pressure overload leads to cardiac fibrosis, the leading cause of heart failure. ADAMTS8 (A disintegrin and metalloproteinase with thrombospondin motifs 8) has been reported to be involved in many fibrosis-related diseases. However, the specific role of ADAMTS8 in cardiac fibrosis caused by myocardial infarction or pressure overload is yet unclear. The present study aimed to explore the function of ADAMTS8 in cardiac fibrosis and its underlying mechanism. ADAMTS8 expression was significantly increased in patients with dilated cardiomyopathy; its expression myocardial infarction and TAC rat models was also increased, accompanied by increased expression of \u03b1-SMA and Collagen1. Adenovirus-mediated overexpression of ADAMTS8 through cardiac\n                    <jats:italic>in situ<\/jats:italic>\n                    injection aggravated cardiac fibrosis and impaired cardiac function in the myocardial infarction rat model. Furthermore,\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies revealed that ADAMTS8 promoted the activation of cardiac fibroblasts; ADAMTS8 acted as a paracrine mediator allowing for cardiomyocytes and fibroblasts to communicate indirectly. Our findings showed that ADAMTS8 could damage the mitochondrial function of cardiac fibroblasts and then activate the PI3K-Akt pathway and MAPK pathways, promoting up-regulation of YAP expression, with EGFR upstream of this pathway. This study systematically revealed the pro-fibrosis effect of ADAMTS8 in cardiac fibrosis and explored its potential role as a therapeutic target for the treatment of cardiac fibrosis and heart failure.\n                  <\/jats:p>","DOI":"10.3389\/fcvm.2022.797137","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:51:15Z","timestamp":1644454275000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["ADAMTS8 Promotes Cardiac Fibrosis Partly Through Activating EGFR Dependent Pathway"],"prefix":"10.3389","volume":"9","author":[{"given":"Yafang","family":"Zha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuowang","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1161\/CIRCRESAHA.117.311045","article-title":"EphrinB2 regulates cardiac fibrosis through modulating the interaction of stat3 and TGF-\u03b2\/Smad3 signaling","volume":"121","author":"Su","year":"2017","journal-title":"Circ Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/nrm3904","article-title":"Remodelling the extracellular matrix in development and disease","volume":"15","author":"Bonnans","year":"2014","journal-title":"Nat Rev Mol Cell Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s11010-016-2849-0","article-title":"Relevance of mouse models of cardiac fibrosis and hypertrophy in cardiac research","volume":"424","author":"Rai","year":"2017","journal-title":"Mol Cell Biochem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.mam.2018.07.001","article-title":"Cardiac fibrosis: cell biological mechanisms, molecular pathways and therapeutic opportunities","volume":"65","author":"Frangogiannis","year":"2019","journal-title":"Mol Aspects Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.yjmcc.2016.03.005","article-title":"Myocyte-fibroblast communication in cardiac fibrosis and arrhythmias: mechanisms and model systems","volume":"94","author":"Pellman","year":"2016","journal-title":"J Mol Cell Cardiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/nrcardio.2009.199","article-title":"Myocardial remodeling after infarction: the role of myofibroblasts","volume":"7","author":"van den Borne","year":"2010","journal-title":"Nat Rev Cardiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1161\/01.CIR.83.6.1849","article-title":"Pathological hypertrophy and cardiac interstitium. 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