RIPK3 mediates renal tubular epithelial cell apoptosis in endotoxin‑induced acute kidney injury.

Content Provider	Europe PMC
Author	Zhang, Shu Li, Ruizhao Dong, Wei Yang, Huan Zhang, Li Chen, Yuanhan Wang, Weidong Li, Chunling Wu, Yanhua Ye, Zhiming Zhao, Xingchen Li, Zhilian Zhang, Mengxi Liu, Shuangxin Liang, Xinling
Copyright Year	2019
Abstract	Renal tubular epithelial cell apoptosis is an important pathological mechanism of septic acute kidney injury (AKI). Endotoxin, also known as lipopolysaccharide (LPS), has a key role in septic AKI and can directly induce tubular epithelial cell apoptosis. The upregulation of receptor-interacting protein kinase 3 (RIPK3) in tubular epithelial cells has been reported in septic AKI, with RIPK3 mediating apoptosis in several cell types. In the present study, the effect of RIPK3 on endotoxin-induced AKI was investigated in mouse tubular epithelial cell apoptosis in vitro and in vivo. It was found that the expression of RIPK3 was markedly increased in endotoxin-induced AKI. Endotoxin-induced AKI and tubular epithelial cell apoptosis could be attenuated by GSK′872, a RIPK3 inhibitor. LPS stimulation also upregulated RIPK3 expression in tubular epithelial cells in a time-dependent manner. Both RIPK3 inhibitor and small interfering RNA (siRNA) targeting RIPK3 reduced LPS-induced tubular epithelial cell apoptosis in vitro. The expression of the proapoptotic protein Bax was induced by LPS and reversed by GSK′872 or RIPK3-siRNA. The present study revealed that RIPK3 mediated renal tubular cell apoptosis in endotoxin-induced AKI. RIPK3 may be a potential target for the prevention of renal tubular cell apoptosis in endotoxin-induced AKI.
ISSN	17912997
Journal	Molecular Medicine Reports
Volume Number	20
PubMed Central reference number	PMC6625383
Issue Number	2
PubMed reference number	31257491
e-ISSN	17913004
DOI	10.3892/mmr.2019.10416
Language	English
Publisher	D.A. Spandidos
Publisher Date	2019-06-24
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Zhang et al.
Subject Keyword	endotoxin acute kidney injury renal tubular epithelial cell apoptosis receptor-interacting protein kinase 3
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Biochemistry Cancer Research Molecular Medicine Oncology