Open AccessTacrolimus alleviates LPS‐induced AKI by inhibiting TLR4/MyD88/NF‐κB signalling in mice
Author(s) -
Hu Xueqing,
Zhou Wenqian,
Wu Shun,
Wang Rui,
Luan Zhiyong,
Geng Xin,
Xu Na,
Zhang Zhaoyong,
Ruan Zhenmin,
Wang Zenghui,
Li Furong,
Yu Chen,
Ren Hongqi
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17108
Subject(s) - tlr4 , acute kidney injury , pharmacology , podocyte , lipopolysaccharide , medicine , sepsis , tacrolimus , kidney , inflammation , cancer research , immunology , transplantation , proteinuria
Lipopolysaccharide (LPS)‐induced sepsis‐associated acute kidney injury (SA‐AKI) is a model of clinical serious care syndrome, with high morbidity and mortality. Tacrolimus (TAC), a novel immunosuppressant that inhibits inflammatory response, plays a pivotal role in kidney diseases. In this study, LPS treated mice and cultured podocytes were used as the models of SA‐AKI in vivo and in vitro , respectively. Medium‐ and high‐dose TAC administration significantly attenuated renal function and renal pathological manifestations at 12, 24 and 48 h after LPS treatment in mice. Moreover, the Toll‐like receptor 4 (TLR4)/myeloid differential protein‐88 (MyD88)/nuclear factor‐kappa (NF‐κB) signalling pathway was also dramatically inhibited by medium‐ and high‐dose TAC administration at 12, 24 and 48 h of LPS treatment mice. In addition, TAC reversed LPS‐induced podocyte cytoskeletal injury and podocyte migratory capability. Our findings indicate that TAC has protective effects against LPS‐induced AKI by inhibiting TLR4/MyD88/NF‐κB signalling pathway and podocyte dysfunction, providing another potential therapeutic effects for the LPS‐induced SA‐AKI.