Reduced expression of MiR-125a-5p aggravates LPS-induced experimental acute kidney injury pathology by targeting TRAF6.

Chao Yang, Cheng Yang, Zhi Huang, Jinxin Zhang, Nuoer Chen, Yingfang Guo, Arshad Zahoor, Ganzhen Deng

Life sciences 2022 Jan 01

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Patients with acute kidney injury (AKI) have higher mortality, and sepsis is among its main causes. MicroRNAs (miRNAs) are essential for regulating kidney function and could have curative potential. This study explored the possibility to treat AKI with miR-125a-5p and reveal the possible mechanism. LPS-induced mouse model and LPS-induced RAW264.7 cell model of AKI were established and treated with miR-125a-5p mimics or inhibitors. Serum creatinine and blood urea were measured to evaluate kidney function. The pathological changes of kidney tissues were detected by H&E and PAS staining technique, and the infiltration of macrophages were observed by immunohistochemistry. RAW264.7 cell viability, TRAF6 and cytokines expressions under LPS stimulation were measured. The role and therapeutic potential of miR-125a-5p were verified in vivo and in vitro after given miR-125a-5p mimics or inhibitors. LPS-induced mice had increasing serum creatinine and urea, and evident pathological changes, including severe tubular dilatation and macrophages infiltration. TRAF6 expression in the kidney was significantly higher, while miR-125a-5p expression was suppressed. MiR-125a-5p targeted TRAF6, and its overexpression deactivated NF-κB signaling pathway, reducing downstream TNF-α, IL-1β and IL-6 expressions. MiR-125a-5p mimics rescued LPS-induced kidney damage and suppressed pro-inflammatory cytokines expression through inhibiting TRAF6/NF-κB axis. We highlighted that miR-125a-5p could inhibit LPS-induced acute inflammation in the kidney through targeting TRAF6/NF-κB axis. These results might contribute to the development of molecular therapy in AKI. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Chao Yang, Cheng Yang, Zhi Huang, Jinxin Zhang, Nuoer Chen, Yingfang Guo, Arshad Zahoor, Ganzhen Deng. Reduced expression of MiR-125a-5p aggravates LPS-induced experimental acute kidney injury pathology by targeting TRAF6. Life sciences. 2022 Jan 01;288:119657