Tacrolimus alleviates LPS-induced AKI by inhibiting TLR4/MyD88/NF-κB signalling in mice.

Abstract

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.

• Authors: Xueqing Hu, Wenqian Zhou, Shun Wu, Rui Wang, Zhiyong Luan, Xin Geng, Na Xu, Zhaoyong Zhang, Zhenmin Ruan, Zenghui Wang, Furong Li, Chen Yu, Hongqi Ren
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 26 Issue 2 Pg. 507-514 (01 2022) ISSN: 1582-4934 [Electronic] England
• PMID: 34889045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Lipopolysaccharides
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• NF-kappa B
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Tacrolimus

Topics

• Acute Kidney Injury (chemically induced, drug therapy, metabolism)
• Animals
• Lipopolysaccharides (pharmacology)
• Mice
• Myeloid Differentiation Factor 88 (metabolism)
• NF-kappa B (metabolism)
• Tacrolimus (pharmacology)
• Toll-Like Receptor 4 (metabolism)