牙髓源性间充质干细胞通过miR-19a-3p/IRF-8/MAPK通路在缺血-再灌注中抑制心肌细胞焦亡。

IF 7.5 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Yi Li, Xiang Wang, Sixian Weng, Chenxi Xia, Xuyang Meng, Chenguang Yang, Ying Guo, Zuowei Pei, Haiyang Gao, Fang Wang
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引用次数: 0

摘要

背景:间充质干细胞(MSCs)对心脏缺血再灌注(I/R)损伤的保护作用已被广泛报道。牙髓源性间充质干细胞(DP-MSCs)对多种疾病有治疗作用,包括糖尿病和肝硬化。本研究旨在确定DP-MSCs对I/R损伤的治疗作用并阐明其潜在机制。方法:采用DP-MSCs或miR-19a-3p模拟物处理心肌I/R损伤模型小鼠。测定梗死体积、纤维化面积、焦亡、炎症水平、心功能。暴露于缺氧再氧化的心肌细胞转染miR-19a-3p模拟物、miR-19a-3p抑制剂或阴性对照。检测细胞凋亡和干扰素调节因子8/丝裂原活化蛋白激酶(IRF-8/MAPK)通路的蛋白表达。结果:DP-MSCs对I/ r损伤小鼠心功能有保护作用,对心肌细胞焦亡有抑制作用。miR-19a-3p上调可保护心脏I/ r损伤小鼠的心功能,抑制心肌细胞焦亡,抑制IRF-8/MAPK信号传导。DP-MSCs通过上调I/R损伤心肌细胞中的miR-19a-3p水平,抑制心肌细胞焦亡和IRF-8/MAPK信号通路。结论:DP-MSCs在I/R条件下通过miR-19a-3p抑制心肌细胞焦亡,保护心功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cardiomyocyte pyroptosis inhibited by dental pulp-derived mesenchymal stem cells via the miR-19a-3p/IRF-8/MAPK pathway in ischemia-reperfusion.

Background: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism.

Methods: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured.

Results: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R.

Conclusion: DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.

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来源期刊
Chinese Medical Journal
Chinese Medical Journal 医学-医学:内科
CiteScore
9.80
自引率
4.90%
发文量
19245
审稿时长
6 months
期刊介绍: The Chinese Medical Journal (CMJ) is published semimonthly in English by the Chinese Medical Association, and is a peer reviewed general medical journal for all doctors, researchers, and health workers regardless of their medical specialty or type of employment. Established in 1887, it is the oldest medical periodical in China and is distributed worldwide. The journal functions as a window into China’s medical sciences and reflects the advances and progress in China’s medical sciences and technology. It serves the objective of international academic exchange. The journal includes Original Articles, Editorial, Review Articles, Medical Progress, Brief Reports, Case Reports, Viewpoint, Clinical Exchange, Letter,and News,etc. CMJ is abstracted or indexed in many databases including Biological Abstracts, Chemical Abstracts, Index Medicus/Medline, Science Citation Index (SCI), Current Contents, Cancerlit, Health Plan & Administration, Embase, Social Scisearch, Aidsline, Toxline, Biocommercial Abstracts, Arts and Humanities Search, Nuclear Science Abstracts, Water Resources Abstracts, Cab Abstracts, Occupation Safety & Health, etc. In 2007, the impact factor of the journal by SCI is 0.636, and the total citation is 2315.
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