Semaphorin 7A interacts with nuclear factor NF-kappa-B p105 via integrin β1 and mediates inflammation.

ABSTRACT: Semaphorin7a (SEMA7A), a membrane-anchored member of the semaphorin protein family, could be involved in a diverse range of immune responses via its receptor integrin β1. Recently, we reported that the SEMA7A^R148W mutation (a gain-of-function mutation, Sema7a^R145W in mice) is a risk factor for progressive familial intrahepatic cholestasis and nonalcoholic fatty liver disease via upregulated membrane localization. In this study, we demonstrated that integrin β1 is a membrane receptor for nuclear factor NF-kappa-B p105 (NF-κB p105) and a critical mediator of inflammation. Integrin β1 could interact with the C-terminal domain of NF-κB p105 to promote p50 generation and stimulate the NF-κB p50/p65 signalling pathway, upregulate TNF-α and IL-1β levels, and subsequently ren

SUBMITTER: Li X 

PROVIDER: S-EPMC9885601 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature