Androgen aggravates liver fibrosis by activation of NLRP3 inflammasome in CCl 4 -induced liver injury mouse model.

Autor: Ma X; College of Animal Science, Southwest University, Chongqing, China.; College of Life Science and Technology, Jinan University, Guangzhou, China., Zhou Y; College of Animal Science, Southwest University, Chongqing, China.; Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, China.; Laboratory Animal Center in College of Animal Science, Southwest University, Chongqing, China., Qiao B; College of Animal Science, Southwest University, Chongqing, China., Jiang S; College of Animal Science, Southwest University, Chongqing, China., Shen Q; Department of Microbiology, Ohio State University, Columbus, Ohio., Han Y; College of Animal Science, Southwest University, Chongqing, China., Liu A; College of Animal Science, Southwest University, Chongqing, China., Chen X; College of Animal Science, Southwest University, Chongqing, China., Wei L; College of Animal Science, Southwest University, Chongqing, China., Zhou L; College of Animal Science, Southwest University, Chongqing, China., Zhao J; College of Animal Science, Southwest University, Chongqing, China.; Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, China.; Laboratory Animal Center in College of Animal Science, Southwest University, Chongqing, China.
Jazyk: angličtina
Zdroj: American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2020 May 01; Vol. 318 (5), pp. E817-E829. Date of Electronic Publication: 2020 Mar 17.
DOI: 10.1152/ajpendo.00427.2019
Abstrakt: Studies have shown that there are differences between the sexes regarding to the occurrence and development of liver diseases, which may be associated with sex hormones. However, the mechanisms behind it are largely unknown. In this study, we first investigated the differences of liver injury between male and female mice, using the CCl 4 -induced liver injury mouse model. It showed that the liver damage of male mice was much more severe than that of female mice. Both the acute injury and fibrosis of the liver were reduced when androgens were depleted by castration of male mice. The vulnerability of male liver was associated with testis endocrine and excessive activation of inflammatory response in the liver. Castrated male mice with testosterone supplementation showed aggravated liver inflammatory response and fibrosis. The activity of NOD-like receptor protein 3 (NLRP3) inflammasome was increased when testosterone supplementation was provided. However, the enhanced inflammatory response and fibrosis due to testosterone supplementation were negated by inhibiting the activation of NLRP3 using the specific small molecule inhibitor MCC950. It suggests that testosterone is a key factor that influences liver injury by regulating the NLRP3 inflammasome activation-mediated inflammatory response.
Databáze: MEDLINE
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