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http://dx.doi.org/10.14348/molcells.2021.0066

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)
Publication Information
Molecules and Cells / v.45, no.3, 2022 , pp. 122-133 More about this Journal
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
atrial fibrillation; cardiac fibroblast proliferation; collagen synthesis; H19; miR-29a-3p; miR-29b-3p;
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