miR-20a-5p is enriched in hypoxia-derived tubular exosomes and protects against acute tubular injury.

Wenjuan Yu, Honghui Zeng, Junzhe Chen, Sha Fu, Qiuyan Huang, Yanchun Xu, Anping Xu, Hui-Yao Lan, Ying Tang

Clinical science (London, England : 1979) 2020 Aug 28

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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. © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Citation

Wenjuan Yu, Honghui Zeng, Junzhe Chen, Sha Fu, Qiuyan Huang, Yanchun Xu, Anping Xu, Hui-Yao Lan, Ying Tang. miR-20a-5p is enriched in hypoxia-derived tubular exosomes and protects against acute tubular injury. Clinical science (London, England : 1979). 2020 Aug 28;134(16):2223-2234