Open AccessRequirement of miR‐9‐dependent regulation of Myocd in PASMC s phenotypic modulation and proliferation induced by hepatopulmonary syndrome rat serum
Author(s) -
Xu Duo,
Gu Jianteng,
Yi Bin,
Chen Lin,
Wang Guansong,
Qian Guisheng,
Lu Kaizhi
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12631
Subject(s) - myocardin , serum response factor , gene knockdown , mef2 , biology , cancer research , phenotype , hepatopulmonary syndrome , microrna , vascular smooth muscle , ectopic expression , microbiology and biotechnology , medicine , endocrinology , transcription factor , cell culture , transplantation , genetics , smooth muscle , enhancer , gene , liver transplantation
Abstract Hepatopulmonary syndrome ( HPS ) is characterized by a triad of severe liver disease, intrapulmonary vascular dilation and hypoxaemia. Pulmonary vascular remodelling ( PVR ) is a key feature of HPS pathology. Our previous studies have established the role of the pulmonary artery smooth muscle cell ( PASMC ) phenotypic modulation and proliferation in HPS ‐associated PVR . Myocardin, a robust transcriptional coactivator of serum response factor, plays a critical role in the vascular smooth muscle cell phenotypic switch. However, the mechanism regulating myocardin upstream signalling remains unclear. In this study, treatment of rat PASMC s with serum drawn from common bile duct ligation rats, which model symptoms of HPS , resulted in a significant increase in miR‐9 expression correlated with a decrease in expression of myocardin and the phenotypic markers SM ‐α‐actin and smooth muscle‐specific myosin heavy chain (SM‐MHC). Furthermore, mi RNA functional analysis and luciferase reporter assay demonstrated that miR‐9 effectively regulated myocardin expression by directly binding to its 3′‐untranslated region. Both the knockdown of miR‐9 and overexpression of myocardin effectively attenuated the HPS rat serum‐induced phenotype switch and proliferation of PASMC s. Taken together, the findings of our present study demonstrate that miR‐9 is required in HPS rat serum‐induced phenotypic modulation and proliferation of PASMC s for targeting of myocardin and that miR‐9 may serve as a potential therapeutic target in HPS .