Myeloid Endoplasmic Reticulum Resident Chaperone GP96 Facilitates Inflammation and Steatosis in Alcohol-Associated Liver Disease.

ABSTRACT: Cellular stress-mediated chaperones are linked to liver macrophage activation and inflammation in alcohol-associated liver disease (ALD). In this study, we investigate the role of endoplasmic reticulum (ER) resident stress chaperone GP96/HSP90B1/GRP94, paralog of the HSP90 family, in ALD pathogenesis. We hypothesize that ER resident chaperone, heat shock protein GP96, plays a crucial role in alcohol-associated liver inflammation and contributes to liver injury. We show high expression of GP96/HSP90B1 and GRP78/HSPA5 in human alcohol-associated hepatitis livers as well as in mouse ALD livers with induction of GP96 prominent in alcohol-exposed macrophages. Myeloid-specific GP96 deficient (M-GP96KO) mice failed to induce alcohol-associated liver injury. Alcohol-fed M-GP96KO mice exhibit signi

SUBMITTER: Ratna A 

PROVIDER: S-EPMC8279472 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature