MiR-21 enhances cardiac fibrotic remodeling and fibroblast proliferation via CADM1/STAT3 pathway

Wei Cao,Jian-Jun Ge,Peng Shi

doi:10.1186/s12872-017-0520-7

Abstract

BackgroundCardiac fibrosis play a key role in the atrial fibrillation pathogenesis but the underlying potential molecular mechanism is still understood. However, potential mechanisms for miR-21 upregulation and its role in cardiac fibrosis remain unclear. The controls cell proliferation and processes fundamental to disease progression.MethodsIn this study, immunohistochemistry, real-time RT-PCR, cell transfection, cell cycle, cell proliferation and Western blot were used, respectively.ResultsHere we have been demonstrated that the tumor suppressor cell adhesion molecule 1 (CADM1) is the potential target of miR-21. Our study revealed that miR-21 regulation of CADM1 expression, which was decreased in cardiac fibroblasts and fibrosis tissue. The cardiac fibroblasts transfected with miR-21 mimic promoted miR-21 overexpression enhanced STAT3 expression and decreased CADM1 expression. Nevertheless, the cardiac fibroblasts transfected with miR-21 inhibitor obtained the opposite expression result. Furthermore, downexpression of miR-21 suppressed cardiac fibroblast proliferation.ConclusionsThese results suggested that miR-21 overexpression promotes cardiac fibrosis via STAT3 signaling pathway by decrease CADM1 expression, indicating miR-21 as an important signaling molecule for cardiac fibrotic remodeling and AF.

Highlights

Cardiac fibrosis play a key role in the atrial fibrillation pathogenesis but the underlying potential molecular mechanism is still understood
cell adhesion molecule 1 (CADM1)/STAT3 signal pathway activation in cardiac fibrotic remodeling and fibroblast Immunohistochemistry assay demonstrated that pSTAT3 and α-SMA protein expression were significantly increased in the model groups compared with the control (Fig. 2a)
Images show α-SMA staining localised selectively to smooth muscle cells lining vessels of SR heart and Atrial fibrillation (AF) heart. b Rat heart tissues RNA was isolated, and STAT3, α-SMA expression were evaluated by qRT-PCR. c Human heart tissues RNA was isolated, and STAT3, α-SMA expression were evaluated by qRT-PCR. d Rat heart tissues RNA and protein was isolated, CADM1 messenger RNAs (mRNAs) expression was evaluated by qRT-PCR, CADM1 expression was analyzed by Western blotting. e Human heart tissues RNA and protein was isolated, CADM1 mRNA expression was evaluated by qRT-PCR, CADM1 expression was analyzed by Western blotting. f Total protein and RNA isolated from 0, 24 and 48 h cultures with TGF-β1 of rat CFs, STAT3, α-SMA and CADM1 expression were analyzed by Western blotting and qRT-PCR

Summary

Introduction

Cardiac fibrosis play a key role in the atrial fibrillation pathogenesis but the underlying potential molecular mechanism is still understood. Potential mechanisms for miR-21 upregulation and its role in cardiac fibrosis remain unclear. Atrial fibrillation (AF) is considered to be an indication of underlying heart disease and is one of the most common cardiac arrhythmia disorders [1]. The molecular mechanisms of cardiac remodeling during atrial fibrillation remain incompletely understood. MicroRNAs (miRs), small endogenous non-coding RNAs, about 19–22 nt functional RNA molecule, play important regulatory roles by sequence-specific base pairing on the 3' untranslated region (3'-UTR) of target messenger RNAs (mRNAs) [5]. The effect of miR-21 on cardiac fibrosis has been well established [8, 9]. The precise function of miR-21 in cardiac fibrosis is still unclear

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Discussion

Conclusion