急性肾损伤
微泡
体外
细胞凋亡
肾
小RNA
体内
外体
肌酐
缺氧(环境)
肾缺血
药理学
急性肾小管坏死
再灌注损伤
医学
缺血
癌症研究
细胞生物学
化学
生物
内科学
生物化学
氧气
有机化学
生物技术
基因
作者
Wenjuan Yu,Honghui Zeng,Junzhe Chen,Sha Fu,Qiuyan Huang,Yanchun Xu,Anping Xu,Hui Y. Lan,Ying Tang
出处
期刊:Clinical Science
[Portland Press]
日期:2020-08-01
卷期号:134 (16): 2223-2234
被引量:37
摘要
Abstract Exosomes have been shown to effectively regulate the biological functions of target cells. Here, we investigated the protective effect and mechanism of hypoxia-induced renal tubular epithelial cells (TECs)-derived exosomes on acute tubular injury. We found that in vitro hypoxia-induced tubular exosomes (Hy-EXOs) were protective in acute tubular injury by promoting TECs proliferation and improving mitochondrial functions. By using exosome miRNA sequencing, we identified miR-20a-5p was abundant and was a key mechanism for the protective effect of Hy-EXOs on tubular injury as up-regulation of miR-20a-5p enhanced but down-regulation of miR-20a-5p inhibited the protective effect of Hy-EXOs on tubular injury under hypoxia conditions. Further study in a mouse model of ischemia–reperfusion-induced acute kidney injury (IRI-AKI) also confirmed this notion as pre-treating mice with the miR-20a-5p agomir 48 h prior to AKI induction was capable of inhibiting IRI-AKI by lowering serum levels of creatinine and urea nitrogen, and attenuating the severity of tubular necrosis, F4/80(+) macrophages infiltration and vascular rarefaction. Mechanistically, the protective effect of miR-20a-5p on acute kidney injury (AKI) was associated with inhibition of TECs mitochondrial injury and apoptosis in vitro and in vivo. In conclusion, miR-20a-5p is enriched in hypoxia-derived tubular exosomes and protects against acute tubular injury. Results from the present study also reveal that miR-20a-5p may represent as a novel therapy for AKI.
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