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微小RNA-22通过靶向p38丝裂原活化蛋白激酶α抑制主动脉夹层血管重塑中血管平滑肌细胞的凋亡。

MicroRNA-22 Inhibits the Apoptosis of Vascular Smooth Muscle Cell by Targeting p38MAPKα in Vascular Remodeling of Aortic Dissection.

作者信息

Xiao Yu, Sun Yudong, Ma Xiang, Wang Chen, Zhang Lei, Wang Jiannan, Wang Guokun, Li Zhenjiang, Tian Wen, Zhao Zhiqing, Jing Qing, Zhou Jian, Jing Zaiping

机构信息

Department of Vascular Surgery, Changhai Hospital, Navy Medical University, Shanghai 200433, China.

Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

出版信息

Mol Ther Nucleic Acids. 2020 Aug 25;22:1051-1062. doi: 10.1016/j.omtn.2020.08.018. eCollection 2020 Dec 4.

Abstract

MicroRNA 22 (miR-22) was found in diverse cardiovascular diseases to have a role in regulating multiple cellular processes. However, the regulatory role of miR-22 in aortic dissection (AD) was still unclear. The miR-22 expression in human aorta was explored. A series of mimic, inhibitor, or small interfering RNA (siRNA) plasmids were delivered into vascular smooth muscle cells (VSMCs) to explore the effects of miR-22 and p38 mitogen-activated protein kinase α (p38MAPKα) in controlling VSMC apoptosis . In addition, a mouse AD model was established, and histopathologic analyses were performed to evaluate the regulatory effects of miR-22. Reduced miR-22 and increased apoptosis of VSMCs was seen in human AD aorta. Downregulation of miR-22 increased the apoptosis of VSMCs . Bioinformatics analyses revealed that p38MAPKα was a target of miR-22. Inhibiting p38MAPKα expression could reverse the apoptosis of VSMCs induced by miR-22 downregulation. Knockdown of miR-22 in the AD mouse model significantly promoted the development of AD. Our data underscore the importance of vascular remodeling and VSMC function in AD. miR-22 may represent a new therapeutic approach for AD by regulating the apoptosis of VSMCs through the MAPK signaling pathway.

摘要

微小RNA 22(miR-22)在多种心血管疾病中被发现参与调节多个细胞过程。然而,miR-22在主动脉夹层(AD)中的调节作用仍不清楚。本研究探索了miR-22在人主动脉中的表达情况。将一系列模拟物、抑制剂或小干扰RNA(siRNA)质粒导入血管平滑肌细胞(VSMC),以探究miR-22和p38丝裂原活化蛋白激酶α(p38MAPKα)在控制VSMC凋亡中的作用。此外,建立了小鼠AD模型,并进行组织病理学分析以评估miR-22的调节作用。在人AD主动脉中观察到miR-22表达降低以及VSMC凋亡增加。miR-22的下调增加了VSMC的凋亡。生物信息学分析表明p38MAPKα是miR-22的一个靶点。抑制p38MAPKα表达可逆转miR-22下调诱导的VSMC凋亡。在AD小鼠模型中敲低miR-22显著促进了AD的发展。我们的数据强调了血管重塑和VSMC功能在AD中的重要性。miR-22可能通过丝裂原活化蛋白激酶(MAPK)信号通路调节VSMC凋亡,从而为AD提供一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e9a/7691156/966aedf10565/fx1.jpg

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