Dongjing Clinical College of Henan University, Henan Province, China.
Department of Cardiology, Xianyang Hospital of Yan'an University, Xianyang, Shaanxi Province, China.
Biosci Rep. 2020 Sep 30;40(9). doi: 10.1042/BSR20201227.
Cardiac fibrosis after myocardial infarction (MI) is a major cause of heart deterioration. Recently, the roles of microRNAs (miRNAs) in various cardiovascular diseases associated with cardiac fibrosis have been extensively investigated. The present study aimed to investigate the role and mechanism of miR-29b-3p in cardiac fibrosis after MI.
miR-29b-3p expression in TGF-β1-activated cardiac fibroblasts (CFs) was detected by qRT-PCR. Cell Counting Kit-8 (CCK-8) and Trans-well assays were performed to evaluate CFs proliferation and migration ability, respectively. Protein expressions of α-SMA, collagen I, collagen III, MMP2, and MMP9 were examined by Western blot assay. Bioinformatics, luciferase, and RNA immunoprecipitation (RIP) assays were carried out to determine whether FOS was targeted by miR-29b-3p.
TGF-β1 treatment dose-dependently curbed miR-29b-3p expression in CFs. miR-29b-3p restrained the promotive impacts of TGF-β1 on CFs proliferation, migration, and differentiation. FOS was affirmed to be a target of miR-29b-3p, elevated expression of FOS reversed the inhibitory effects of miR-29b-3p on cell proliferation, migration, and differentiation in TGF-β1-activated CFs.
miR-29b-3p degraded the pro-fibrosis effect induced by TGF-β1 via targeting FOS, providing a prospective therapeutic avenue for cardiac fibrosis after MI.
心肌梗死后的心脏纤维化是心脏恶化的主要原因。最近,microRNAs(miRNAs)在与心脏纤维化相关的各种心血管疾病中的作用得到了广泛的研究。本研究旨在探讨 miR-29b-3p 在心肌梗死后心脏纤维化中的作用和机制。
采用 qRT-PCR 检测 TGF-β1 激活的心肌成纤维细胞(CFs)中 miR-29b-3p 的表达。采用细胞计数试剂盒-8(CCK-8)和 Trans-well 测定分别评估 CFs 的增殖和迁移能力。Western blot 检测 α-SMA、胶原 I、胶原 III、MMP2 和 MMP9 的蛋白表达。采用生物信息学、荧光素酶和 RNA 免疫沉淀(RIP)实验确定 FOS 是否是 miR-29b-3p 的靶标。
TGF-β1 处理呈剂量依赖性抑制 CFs 中 miR-29b-3p 的表达。miR-29b-3p 抑制了 TGF-β1 对 CFs 增殖、迁移和分化的促进作用。FOS 被确认为 miR-29b-3p 的靶标,FOS 的高表达逆转了 miR-29b-3p 在 TGF-β1 激活的 CFs 中对细胞增殖、迁移和分化的抑制作用。
miR-29b-3p 通过靶向 FOS 降解 TGF-β1 诱导的促纤维化作用,为心肌梗死后心脏纤维化提供了一种有前景的治疗途径。