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.

miRNA profiling of urinary exosomes to assess the progression of acute kidney injury

“…Except mir-148a-3p, we were able to retrieve experimentally validated mRNA targets using miRTarBase 22 . For collected experimentally validated targets, see references in 23 – 34 for targets of miR-9a-5p 35 – 39 ; for miR-141-3p 38 , 40 – 46 ; for miR-200a-3p 38 , 44 , 47 ; for miR-200c-3p 38 ; for miR-429. Overlapped targets were represented graphically as a Venn diagram.…”

MiR145-5p inhibits proliferation of PMVECs via PAI-1 in experimental hepatopulmonary syndrome rat pulmonary microvascular hyperplasia

“…It has been reported that miRNA association results in translational repression, frequently accompanied by a considerable degradation of mRNAs by a non-RNAi mechanism (Filipowicz et al, 2008). Previous studies and our initial research have demonstrated that several miRNAs have roles in regulating the pathology of HPS, including miR-206, miR-199a-5p and miR-9 (Chen et al, 2014; Gao et al, 2015; Xu et al, 2015). To date, these findings are related to miRNAs regulating PASMC phenotypic modulation and proliferation.…”

Aberrant Expression of microRNA-9 Contributes to Development of Intracranial Aneurysm by Suppressing Proliferation and Reducing Contractility of Smooth Muscle Cells

“…Using the online miRNA database, we found that MYOCD is a virtual target of miR-9, and MYOCD has been reported to be involved in the pathogenesis of IA by regulating the contractility of smooth muscle cells [14]. In the present study we explored the relationship between miR-9 and MYOCD, finding that downregulation of MYOCD caused by upregulation of miR-9 leads to the development of IA.…”