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miR-129-5p alleviates LPS-induced acute kidney injury via targeting HMGB1/TLRs/NF-kappaB pathway

Huang, Xin, Hou, Xiangping, Chuan, Libo, Wei, Shutao, Wang, Jingrong, Yang, Xiaohua, Ru, Jin·2020·International Immunopharmacology

DOI 10.1016/j.intimp.2020.107016

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Abstract

Introduction The present study aimed to investigate whether miR-129-5p can regulate high-mobility group box protein 1 (HMGB1)-modulated TLRs/NF-kappaB inflammatory pathway that contributed to lipopolysaccharide (LPS)-induced podocyte apoptosis and acutekidneyinjury (AKI). Material and methods In vitro and in vivo models of sepsis were simulated using LPS-administrated podocytes and mice, respectively. The effects of LPS, mR-129-5p mimics and short hairpin RNA of HMGB1 (sh-HMGB1) on podocyte apoptosis were monitored using TUNEL staining. Protein expression was measured using western blotting. Survival outcomes were analyzed in septic mice with agomir-mR-129-5p administration. Results We observed that stimulation of podocytes with LPS significantly inhibits the expression of miR-129-5p, and overexpression of miR-129-5p protects against LPS-induced podocyte damage, over-activation of inflammatory response and apoptosis. In a mouse model, agomir-miR-129-5p administration significantly improves the survival outcomes in septic mice and LPS-induced AKI. Mechanically, LPS-induced the elevation of HMGB1, TLR2, TLR4 and nuclear NF-κB protein expression in vitro and in vivo are restrained by the overexpression of miR-129-5p. Conclusions Overexpression of miR-129-5p protects against LPS-induced podocyte apoptosis, inflammation and AKI in vivo and in vitro models of sepsis. The underlying molecular mechanism is mediated via attenuating HMGB1/TLRs/NF-κB signaling axis modulated inflammator…

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Authors: Huang, X., Hou, X., Chuan, L., Wei, S., Wang, J., Yang, X., & Ru, J.
Venue: International Immunopharmacology
Publisher: Elsevier BV
Published: 2020-12
Volume: 89
Pages: 107016
ISSN: 1567-5769
DOI: 10.1016/j.intimp.2020.107016
Cited by: 47
References: 46
Language: en
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)

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miR-129-5p alleviates LPS-induced acute kidney injury via targeting HMGB1/TLRs/NF-kappaB pathway

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