β-arrestin-2 enhances intestinal epithelial apoptosis in necrotizing enterocolitis.

ABSTRACT: Apoptosis among intestinal epithelial cells contributes to necrotizing enterocolitis (NEC), a severe intestinal disease that particularly affects premature infants. β-arrestin-2, an important regulator of G-protein-coupled receptors, is expressed in intestinal epithelial cells, where its activation promotes apoptosis. We found that β-arrestin-2 was overexpressed in both human and murine NEC samples. β-arrestin-2-deficient mice were protected from endoplasmic reticulum stress and NEC development. The endoplasmic reticulum-resident chaperone BiP was found to promote intestinal epithelial cell survival. Pretreatment of intestinal epithelial cells or mice with the BiP inhibitor HA15 increased cell apoptosis and promoted NEC development. β-arrestin-2 bound to BiP and promoted its polyubiquitina

SUBMITTER: Fu D 

PROVIDER: S-EPMC6814604 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature