miR-29b ameliorates atrial fibrosis in rats with atrial fibrillation by targeting TGFβRΙ and inhibiting the activation of Smad-2/3 pathway.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2022-04-01 Epub Date: 2022-03-24 DOI:10.1007/s10863-022-09934-7

Xinyuan Han, Shunda Wang, Zhijun Yong, Xueting Zhang, Xuanqi Wang

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引用次数: 6

Abstract

Objective: Atrial fibrillation (AF) is a major cause of stroke with lifetime risks. microRNAs (miRNAs) are associated with AF attenuation, yet the mechanism remains unknown. This study investigated the functional mechanism of miR-29b in atrial fibrosis in AF.

Methods: The AF rat model was established by a 7-day intravenous injection of Ach-CaCl₂ mixture. AF rats were injected with adeno-associated virus (AAv)-miR-29b and TGFβRΙ overexpression plasmid. AF duration was recorded by electrocardiogram. Atrial fibrosis was observed by Masson staining. Expressions of COL1A1, COL3A1, TGFβRΙ, TGFβΙ, miR-29b and Smad-2/3 pathway-related proteins in atrial tissues were detected by RT-qPCR and Western blot. Binding sites of miR-29b and TGFβRΙ were predicted and their target relationship was verified by dual-luciferase reporter assay.

Results: miR-29b was poorly expressed and expressions of COL1A1, COL3A1, TGFβRΙ, and TGFβ1 were increased in atrial tissues of AF rats. miR-29b overexpression alleviated atrial fibrosis, reduced expressions of COL1A1, COL3A1, and TGFβ1, and shortened AF duration in AF rats. TGFβRΙ was highly expressed in atrial tissues of AF rats. miR-29b targeted TGFβRΙ. TGFβRΙ overexpression overcame the improving effect of miR-29b overexpression on AF. miR-29b overexpression decreased ratios of p-Smad-2/3 and Smad-2/3 and inhibited the Smad-2/3 pathway.

Conclusion: miR-29b might mitigate atrial fibrosis in AF rats by targeting TGFβRΙ and inhibiting the Smad-2/3 pathway.

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miR-29b通过靶向TGFβRΙ和抑制Smad-2/3通路的激活来改善房颤大鼠的心房纤维化。

目的:心房颤动(AF)是卒中的主要原因，具有终生风险。microRNAs (miRNAs)与AF衰减有关，但其机制尚不清楚。本研究探讨miR-29b在房颤心房纤维化中的作用机制。方法:采用静脉注射ache - cacl2混合物7 d建立房颤大鼠模型。用腺相关病毒(AAv)-miR-29b和TGFβRΙ过表达质粒注射AF大鼠。心电图记录AF持续时间。马松染色观察心房纤维化。RT-qPCR和Western blot检测心房组织中COL1A1、COL3A1、TGFβRΙ、TGFβΙ、miR-29b和Smad-2/3通路相关蛋白的表达。预测miR-29b和TGFβRΙ的结合位点，并通过双荧光素酶报告基因实验验证其靶标关系。结果:AF大鼠心房组织中miR-29b表达低，COL1A1、COL3A1、TGFβRΙ、tgf - β1表达升高。miR-29b过表达可减轻房颤大鼠心房纤维化，降低COL1A1、COL3A1和TGFβ1的表达，缩短房颤持续时间。TGFβRΙ在房颤大鼠心房组织中高表达。miR-29b靶向TGFβRΙ。TGFβRΙ过表达克服了miR-29b过表达对af的改善作用。miR-29b过表达降低了p-Smad-2/3和Smad-2/3的比例，抑制了Smad-2/3通路。结论:miR-29b可能通过靶向TGFβRΙ和抑制Smad-2/3通路减轻房颤大鼠心房纤维化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464