Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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LncRNA H19 Drives Proliferation of Cardiac Fibroblasts and Collagen Production via Suppression of the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β Axis

  • Guo, Feng (Department of Cardiology, Shanghai Electric Power Hospital) ;
  • Tang, Chengchun (Department of Cardiology, Zhongda Hospital Southeast University) ;
  • Huang, Bo (Department of Cardiology, Shanghai Electric Power Hospital) ;
  • Gu, Lifei (Department of Cardiology, Shanghai Electric Power Hospital) ;
  • Zhou, Jun (Department of Cardiology, Shanghai Electric Power Hospital) ;
  • Mo, Zongyang (Department of Cardiology, Shanghai Electric Power Hospital) ;
  • Liu, Chang (Department of Cardiology, Shanghai Electric Power Hospital) ;
  • Liu, Yuqing (Department of Emergency, Naval Characteristic Medical Center Affiliated to Shanghai, Naval Medical University)
  • Received : 2021.03.07
  • Accepted : 2021.09.29
  • Published : 2022.03.31
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Abstract

The aim of this study was to investigating whether lncRNA H19 promotes myocardial fibrosis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis. Patients with atrial fibrillation (AF) and healthy volunteers were included in the study, and their biochemical parameters were collected. In addition, pcDNA3.1-H19, si-H19, and miR-29a/b-3p mimic/inhibitor were transfected into cardiac fibroblasts (CFs), and proliferation of CFs was detected by MTT assay. Expression of H19 and miR-29a/b-3p were detected using real-time quantitative polymerase chain reaction, and expression of α-smooth muscle actin (α-SMA), collagen I, collagen II, matrix metalloproteinase-2 (MMP-2), and elastin were measured by western blot analysis. The dual luciferase reporter gene assay was carried out to detect the sponging relationship between H19 and miR-29a/b-3p in CFs. Compared with healthy volunteers, the level of plasma H19 was significantly elevated in patients with AF, while miR-29a-3p and miR-29b-3p were markedly depressed (P < 0.05). Serum expression of lncRNA H19 was negatively correlated with the expression of miR-29a-3p and miR-29b-3p among patients with AF (rs = -0.337, rs = -0.236). Moreover, up-regulation of H19 expression and down-regulation of miR-29a/b-3p expression facilitated proliferation and synthesis of extracellular matrix (ECM)-related proteins. SB431542 and si-VEGFA are able to reverse the promotion of miR-29a/b-3p on proliferation of CFs and ECM-related protein synthesis. The findings of the present study suggest that H19 promoted CF proliferation and collagen synthesis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis, and provide support for a potential new direction for the treatment of AF.

Keywords

Acknowledgement

This work was financially supported by the National Natural Science Foundation of China (81970237).

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