Plasma-derived extracellular vesicles transfer microRNA-130a-3p to alleviate myocardial ischemia/reperfusion injury by targeting ATG16L1
Plasma-derived extracellular vesicles transfer microRNA-130a-3p to alleviate myocardial ischemia/reperfusion injury by targeting ATG16L1
复制标题
血浆来源的细胞外囊泡转移 microRNA-130a-3p 通过靶向 ATG16L1 减轻心肌缺血/再灌注损伤
DOI：
10.1007/s00441-022-03605-0
复制
发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Lianggeng Gong
中科院分区：
文献类型：
--
作者：
Sisi Yu;Xuepei Tang;Tian Zheng;Shuhao Li;Haibo Ren;Hailong Wu;Fei Peng;Lianggeng Gong
细胞外囊泡（EVs）作为调节性物质，通过转运包括microrna （mirna）在内的多种物质参与心肌缺血/再灌注（I/R）损伤。目前的研究旨在揭示携带miR-130a-3p的血浆源性ev对心肌I/R损伤的潜在参与。用中度内质网应激诱导大鼠，然后分离血浆源性ev。然后，建立I/R大鼠模型和缺氧/再氧化（H/R）心肌细胞模型，模拟心肌I/R损伤环境，发现miR-130a-3p丰富表达。证实miR-130a-3p在心肌细胞中靶向并负调控自噬相关的16-like 1 （ATG16L1）。基于共培养系统，血浆来源的ev传递miR-130a-3p保护H/ r暴露的心肌细胞免受H/ r诱导的过度心肌细胞自噬、炎症和损伤，改善心功能障碍以及心肌I/ r诱导的心功能障碍和组织损伤。发现装载ev的miR-130a-3p的功能作用机制依赖于其与ATG16L1的靶向关系。携带ev的miR-130a-3p的保护作用在大鼠模型中进一步重现，并通过改善心功能、组织损伤、心肌纤维化和心肌梗死进行体内验证。总之，经血浆源性ev穿梭的miR-130a-3p被证明可以减轻过度的成心肌细胞自噬，改善心肌I/R损伤。
Extracellular vesicles (EVs) are implicated in myocardial ischemia/reperfusion (I/R) injury as modulators by shuttling diverse cargoes, including microRNAs (miRNAs). The current study was initiated to unravel the potential involvement of plasma-derived EVs carrying miR-130a-3p on myocardial I/R injury. Rats were induced with moderate endoplasmic reticulum stress, followed by isolation of plasma-derived EVs. Then, an I/R rat model and hypoxia/reoxygenation (H/R) cardiomyoblast model were established to simulate a myocardial I/R injury environment where miR-130a-3p was found to be abundantly expressed. miR-130a-3p was confirmed to target and negatively regulate autophagy-related 16-like 1 (ATG16L1) in cardiomyoblasts. Based on a co-culture system, miR-130a-3p delivered by EVs derived from plasma protected H/R-exposed cardiomyoblasts against H/R-induced excessive cardiomyoblast autophagy, inflammation, and damage, improving cardiac dysfunction as well as myocardial I/R-induced cardiac dysfunction and tissue injury. The mechanism underlying the functional role of EVs-loaded miR-130a-3p was found to be dependent on its targeting relation with ATG16L1. The protective action of EV-carried miR-130a-3p was further re-produced in a rat model serving as in vivo validation as evidenced by improved cardiac function, tissue injury, myocardial fibrosis, and myocardial infarction. Collectively, miR-130a-3p shuttled by plasma-derived EVs was demonstrated to alleviate excessive cardiomyoblast autophagy and improve myocardial I/R injury.
登录
查看更多内容
影响因子：
9.5
作者：
Sassoon DJ;Goodwill AG;Noblet JN;Conteh AM;Herring BP;McClintick JN;Tune JD;Mather KJ
通讯作者：
Mather KJ
影响因子：
5.2
作者：
Tan, Jiaying;Shen, Jun;Sun, Tao
通讯作者：
Sun, Tao
组成型活性 MEK1 通过 ERK1/2 信号通路对 H2O2 诱导的心肌细胞凋亡和自噬的心脏保护作用
DOI：
10.1016/j.bbrc.2019.03.008
发表时间：
2019-04-23
影响因子：
3.1
作者：
Sun, Ming-Hui;Chen, Xiao-Cui;Chen, Bang-Dang
通讯作者：
Chen, Bang-Dang
影响因子：
4.6
作者：
Neri M;Riezzo I;Pascale N;Pomara C;Turillazzi E
通讯作者：
Turillazzi E
心肌缺血/再灌注期间 H2O2 的有害作用和保护作用之间的浓度依赖性角力
影响因子：
9
作者：
Wang ZH;Liu JL;Wu L;Yu Z;Yang HT
通讯作者：
Yang HT