title: Requirement of miR-9-dependent regulation of Myocd in PASMCs phenotypic modulation and proliferation induced by hepatopulmonary syndrome rat serum.
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 PASMCs 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, miRNA 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 PASMCs. Taken together, the findings of our present study demonstrate that miR-9 is required in HPS rat serum-induced phenotypic modulation and proliferation of PASMCs for targeting of myocardin and that miR-9 may serve as a potential therapeutic target in HPS.
authors.affiliation: Department of Anaesthesia, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Anaesthesia, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jian-teng
authors.initials: JT
authors.lastname: Gu
authors.affiliation: Department of Anaesthesia, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.affiliation: Department of Anaesthesia, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Guan-song
authors.initials: GS
authors.lastname: Wang
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Gui-sheng
authors.initials: GS
authors.lastname: Qian
authors.affiliation: Department of Anaesthesia, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Kai-zhi
authors.initials: KZ
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020065:Hepatopulmonary Syndrome / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011651:Pulmonary Artery / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D000099251:Myocardin
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000099251:Myocardin; C582333:MIRN9 microRNA, rat
keywords: Myocd; hepatopulmonary syndrome; microRNA; pulmonary artery smooth muscle cells