Myeloid Nrf2 deficiency aggravates non-alcoholic steatohepatitis progression by regulating YAP-mediated NLRP3 inflammasome signaling.

ABSTRACT: Nuclear-erythroid-2-related factor 2 (Nrf2) is involved in the pathogenesis of different liver diseases. Herein, we first demonstrated that Nrf2 expression was diminished in nonalcoholic steatohepatitis (NASH) liver macrophages. In myeloid Nrf2-deficiency mice, aggravated liver steatosis and inflammation in high-fat-diet (HFD)-fed mice were observed compared with the chow-diet group. Moreover, the increasing inflammatory cytokines influenced the lipid metabolism in hepatocytes in vivo and in vitro. Further study showed Nrf2 regulated reactive-oxygen-species-mediated Hippo-yes-associated protein (YAP) signaling, which in turn modulated the NLRP3 inflammasome activation. Administration of YAP activator also significantly ablated the lipid accumulation and inhibited the NLRP3 activatio

SUBMITTER: Wang P 

PROVIDER: S-EPMC8141901 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature