miR-29b ameliorates atrial fibrosis in rats with atrial fibrillation by targeting TGF beta R Iota and inhibiting the activation of Smad-2/3 pathway

被引：19
作者：
Han, Xinyuan [1 ]
Wang, Shunda [1 ]
Yong, Zhijun [1 ]
Zhang, Xueting [1 ]
Wang, Xuanqi [1 ]
机构：
[1] Shaanxi Prov Peoples Hosp, Dept Rehabil Med, 256 Youyi West Rd, Xian 710068, Shaanxi, Peoples R China
来源：
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES | 2022年 / 54卷 / 02期
关键词：
Atrial fibrillation; Atrial fibrosis; miR-29b; TGF beta R Iota; Smad-2/3; COL1A1; COL3A1; TGF beta 1; GROWTH-FACTOR-BETA; OXIDATIVE STRESS; EXPRESSION; PATHOPHYSIOLOGY; OVEREXPRESSION; EPIDEMIOLOGY; HYPERTROPHY; MECHANISMS; RECEPTORS;
D O I：
10.1007/s10863-022-09934-7
中图分类号：
Q6 [生物物理学];
学科分类号：
071011 ;
摘要：
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 TGF beta RI overexpression plasmid. AF duration was recorded by electrocardiogram. Atrial fibrosis was observed by Masson staining. Expressions of COL1A1, COL3A1, TGF beta RI, TGF beta I, 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 TGF beta RI were predicted and their target relationship was verified by dual-luciferase reporter assay. Results miR-29b was poorly expressed and expressions of COL1A1, COL3A1, TGF beta RI, and TGF beta 1 were increased in atrial tissues of AF rats. miR-29b overexpression alleviated atrial fibrosis, reduced expressions of COL1A1, COL3A1, and TGF beta 1, and shortened AF duration in AF rats. TGF beta RI was highly expressed in atrial tissues of AF rats. miR-29b targeted TGF beta RI. TGF beta R Iota 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 TGF beta RI and inhibiting the Smad-2/3 pathway.
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页码：81 / 91
页数：11
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