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Androgen receptor regulates cardiac fibrosis in mice with experimental autoimmune myocarditis by increasing microRNA-125b expression

Author:
Wang, Ya, Ma, Wenhan, Lu, Shuai, Yan, LianHua, Hu, Fen, Wang, ZhaoHui, Cheng, Bo
Source:
Biochemical and biophysical research communications 2018 v.506 no.1 pp. 130-136
ISSN:
0006-291X
Subject:
androgen receptors, cardiomyopathy, collagen, fibrosis, inflammation, mice, myocarditis, patients, therapeutics
Abstract:
Cardiac fibrosis is an important cardiac remodeling event in the development of inflammation dilated cardiomyopathy (iDCM). We have previously observed that degradation enhancer of androgen receptor (ASC-J9®) could improve cardiac inflammation and fibrosis. Using Primary CFs, we demonstrated that ASC-J9® attenuates the expression of miR-125b, which subsequently inhibits the generation of collagen. In contrast, overexpressed AR in CFs induced collagen production, increases mir-125b.We also found that inhibition of miR-125b attenuates fibrosis which induced by the overexpression of AR. Our results indentify the functional role for AR as a regulator of cardiac fibrosis due to myocarditis and further show that AR exerts its effect by increasing microRNA-125b expression. Treatment with degradation enhancer of AR limits cardiac fibrosis in iDCM, thereby providing potentially a therapeutic approach for patients with iDCM.
Agid:
6175679