{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T02:00:43Z","timestamp":1769738443137,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T00:00:00Z","timestamp":1570492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>(Pro)renin receptor (PRR), a novel member of the renin\u2013angiotensin system, participates in various cardiovascular diseases. However, the role of PRR in alcoholic cardiomyopathy (<jats:styled-content style=\"fixed-case\">ACM<\/jats:styled-content>), which is caused by alcohol intake and manifests as myocardial damage and cardiac dysfunction, remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content> gene silencing was achieved by transfecting recombinant adenovirus expressing anti\u2010<jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content> short hairpin <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content>\u2010sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>). In vitro, primary rat cardiac fibroblasts (<jats:styled-content style=\"fixed-case\">CF<\/jats:styled-content>s) were cultured with the stimulation of alcohol (200\u00a0mM), with or without <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content>\u2010sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>98059. Immunofluorescence, <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>, and Western blot were used to measure the protein and messenger (<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>) expression of <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content>, fibrotic factors, and members of related signaling pathways. In vivo, Wistar rats were fed a diet containing 9% (v\/v) alcohol or a normal diet for 3\u00a0months, with or without <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content>\u2010sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>. Sirius Red staining, immunohistochemical staining, and toluidine blue staining were used to evaluate myocardial fibrosis, oxidative stress, and inflammation response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alcohol markedly increased <jats:styled-content style=\"fixed-case\">PRR mRNA<\/jats:styled-content> and protein expression in a time\u2010 and concentration\u2010dependent manner in <jats:styled-content style=\"fixed-case\">CF<\/jats:styled-content>s. The increased expression of fibrotic factors induced by alcohol was prevented by <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content>\u2010sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>98059. Moreover, <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content>\u2010sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> decreased the phosphorylation of extracellular regulated protein kinases (ERK) 1\/2 in <jats:styled-content style=\"fixed-case\">CF<\/jats:styled-content>s. Furthermore, <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content>\u2010sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> decreased cardiac fibrosis, reduced oxidative stress, and alleviated inflammation response in the myocardial tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results show that <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 signaling was involved in the development of <jats:styled-content style=\"fixed-case\">ACM<\/jats:styled-content> and that <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content> could be a new target for the treatment of ACM.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14188","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T13:47:26Z","timestamp":1568036846000},"page":"2344-2353","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["(Pro)renin Receptor is Involved in Myocardial Damage in Alcoholic Cardiomyopathy"],"prefix":"10.1111","volume":"43","author":[{"given":"Jie","family":"Xiong","sequence":"first","affiliation":[{"name":"From the Department of Cardiology Shandong Provincial Hospital Affiliated to Shandong University Jinan China"},{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine Department of Cardiology Qilu Hospital of Shandong University Jinan 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and Chinese Academy of Medical Sciences The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine Department of Cardiology Qilu Hospital of Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiran","family":"Yu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology Shandong Provincial Hospital Affiliated to Shandong University Jinan China"},{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine Department of Cardiology Qilu Hospital of Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology Shandong Provincial Hospital 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