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Intracellular complement activation in podocytes aggravates immune kidney injury in trichloroethylene-sensitized mice

Yang, Xiaodong, Jiang, Wei, Huang, Meng, Dai, Yuying, Li, Bodong, Wang, Xian, Yu, Yun, Shen, Tong, Wu, Changhao and Zhu, Qixing (2020) Intracellular complement activation in podocytes aggravates immune kidney injury in trichloroethylene-sensitized mice The Journal of Toxicological Sciences.

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Abstract

Trichloroethylene (TCE) as a common organic solvent in industrial production can cause occupational medicamentosa-like dermatitis (OMDT) in some exposed workers. In addition to systemic skin damage, OMDT is also accompanied by severe kidney injury. Our previous studies show that complement(C) plays an important role in immune kidney injury caused by TCE. Specifically, C3 is mainly deposited on glomeruli. Recent studies have found that intracellular complement can be activated by cathepsin L(CTSL) and exert a series of biological effects. The purpose of this study was to explore where C3 on glomeruli comes from and what role it plays. A BALB/c mouse model of skin sensitization induced by TCE in the presence or absence of CTSL inhibitor(CTSLi,10mg/kg). In TCE sensitization-positive mice, C3 was mainly expressed on podocytes and the expression of CTSL significantly increased in podocytes. Kidney function test and related indicators showed abnormal glomerular filtration and transmission electron microscopy revealed ultrastructure damage to podocytes. These lesions were alleviated in TCE/CTSLi positive mice. These results provide the first evidence that in TCE-induced immune kidney injury, intracellular complement in podocytes can be over-activated by CTSL and aggravates podocytes injury, thereby damaging glomerular filtration function. Intracellular complement activation and cathepsin L in podocytes may be a potential target for treating immune kidney injury induced by TCE.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Yang, Xiaodong
Jiang, Wei
Huang, Meng
Dai, Yuying
Li, Bodong
Wang, Xian
Yu, Yun
Shen, Tong
Wu, ChanghaoC.Wu@surrey.ac.uk
Zhu, Qixing
Date : 2020
Funders : Biotechnology and Biological Sciences Research Council (BBSRC), National Institute of Aging
Copyright Disclaimer : © The authors 2020.
Uncontrolled Keywords : Trichloroethylene; Kidney; Immune injury; Podocytes; Intracellular complement; Cathepsin L
Related URLs :
Depositing User : Clive Harris
Date Deposited : 07 Oct 2020 17:46
Last Modified : 07 Oct 2020 17:46
URI: http://epubs.surrey.ac.uk/id/eprint/858719

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