miR-29b 通过靶向 TGFβRΙ 并抑制 Smad-2/3 通路的激活来改善心房颤动大鼠的心房纤维化。
miR-29b ameliorates atrial fibrosis in rats with atrial fibrillation by targeting TGFβRΙ and inhibiting the activation of Smad-2/3 pathway.
机构信息
Department of Rehabilitation Medicine, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Xi'an, 710068, Shaanxi Province, China.
出版信息
J Bioenerg Biomembr. 2022 Apr;54(2):81-91. doi: 10.1007/s10863-022-09934-7. Epub 2022 Mar 24.
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-CaCl 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.
目的
心房颤动（AF）是中风的主要原因，具有终生风险。 microRNAs（miRNAs）与 AF 衰减有关，但机制尚不清楚。本研究探讨了 miR-29b 在 AF 中心房纤维化中的功能机制。
方法
通过 7 天静脉注射 Ach-CaCl 混合物建立 AF 大鼠模型。AF 大鼠注射腺相关病毒（AAv）-miR-29b 和 TGFβRΙ 过表达质粒。通过心电图记录 AF 持续时间。通过 Masson 染色观察心房纤维化。通过 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检测验证其靶关系。
结果
miR-29b 表达降低，AF 大鼠心房组织中 COL1A1、COL3A1、TGFβRΙ 和 TGFβ1 的表达增加。miR-29b 过表达减轻了 AF 大鼠的心房纤维化，降低了 COL1A1、COL3A1 和 TGFβ1 的表达，并缩短了 AF 大鼠的 AF 持续时间。AF 大鼠心房组织中 TGFβRΙ 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 的比值，并抑制了 Smad-2/3 通路。
结论
miR-29b 可能通过靶向 TGFβRΙ 并抑制 Smad-2/3 通路减轻 AF 大鼠的心房纤维化。
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