Androgen aggravates liver fibrosis by activation of NLRP3 inflammasome in CCl4 induced liver injury mouse model.

In this study, we first investigated the differences of liver injury between male and female mice, using the CCl4 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 NLRP3 inflammasome activation mediated inflammatory response. PMID: 32182125 [PubMed - as supplied by publisher]
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research