CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation.

ABSTRACT: Intestinal stem cells (ISCs) at the crypt base contribute to intestinal homeostasis through a balance between self-renewal and differentiation. However, the molecular mechanisms regulating this homeostatic balance remain elusive. Here we show that the matricellular protein CCN1/CYR61 coordinately regulates ISC proliferation and differentiation through distinct pathways emanating from CCN1 interaction with integrins α_vβ₃/α_vβ₅. Mice that delete Ccn1 in Lgr5 + ISCs or express mutant CCN1 unable to bind integrins α_vβ₃/α_vβ₅ exhibited exuberant ISC expansion and enhanced differentiation into secretory cells at the expense of absorptive enterocytes in the small intestine, leading to nutrient malabsorption. Ana

SUBMITTER: Won JH 

PROVIDER: S-EPMC9166801 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature