Effect of miR-29b on the Proliferation and Apoptosis of Pulmonary Artery Smooth Muscle Cells by Targeting Mcl-1 and CCND2.

Juan Chen,Yongwei Zhang,Yanping Li,Yun Li,Lijian Xie,Jianyi Wang,Tingting Xiao

doi:10.1155/2018/6051407

Abstract

The proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) are considered to be key steps in the progression of pulmonary arterial hypertension (PAH). MicroRNAs (e.g., miR-29b) have been identified in various diseases to be critical modulators of cell growth and apoptosis by targeting Mcl-1 and CCND2. However, the role of miR-29b in PAH remains unknown. So we try to investigate the effect of miR-29b on Mcl-1 and CCND2 protein in PASMCs, analyze the effect of miR-29b on the proliferation of PASMCs, and explore the significance of miR-29b in the proliferation, apoptosis, and gene therapy of PAH. It was observed that gene chip analysis showed miR-29b expression in pulmonary artery tissue. The expression of miR-29b was significantly reduced in PAH model mice. MiR-29b inhibited the proliferation of PASMCs and promoted the apoptosis of PASMCs. Mechanically, miR-29b could inhibit the expression of Mcl-1 and CCND2 protein and silenced Mcl-1 and CCND2 could abolish the change of proliferation and apoptosis of PASMCs. These results demonstrate that miR-29b suppressed cellular proliferation and promoted apoptosis of PASMCs, possibly through the inhibition of Mcl-1 and CCND2. Therefore, miR-29b may serve as a useful therapeutic tool to treat PAH.

Highlights

Pulmonary arterial hypertension (PAH) is a devastating disease which leads to right ventricular hypertrophy, progressive heart failure, and potentially death [1]
Our results demonstrated a significant downregulation of Mcl-1 and CCND2 in the pulmonary artery smooth muscle cells (PASMCs) transfected with the miR-29b mimic (Figure 3(c))
MiRNAs are a class of small (19–25 nucleotides) noncoding and highly conserved single-stranded RNAs that repress protein translation through binding to the 3󸀠 UTR of their target mRNAs in a sequence-specific manner. They are important for the regulation of cellular proliferation, cycle, differentiation, survival, and apoptosis [18]

Summary

Introduction

Pulmonary arterial hypertension (PAH) is a devastating disease which leads to right ventricular hypertrophy, progressive heart failure, and potentially death [1]. The pathology of PAH is characterized by pulmonary vasoconstriction, in situ thrombosis, and vessel remodeling. Vessel remodeling is associated with enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs) [2, 3]. MicroRNAs (miRNAs) have been identified as endogenous noncoding small RNAs, which contain 19–25 nucleotides and are involved in the posttranscription regulation of gene expression [4]. Studies have confirmed that the deregulated expression of miRNAs may be involved in the pathogenesis of numerous cardiovascular diseases [5]. MiR-1, miR145, and miR-221/222 can play an important role in the proliferation and migration of smooth muscle cells [7,8,9]

Methods

Results

Conclusion