NOX1-dependent redox signaling potentiates colonic stem cell proliferation to adapt to the intestinal microbiota by linking EGFR and TLR activation.

ABSTRACT: The colon epithelium is a primary point of interaction with the microbiome and is regenerated by a few rapidly cycling colonic stem cells (CSCs). CSC self-renewal and proliferation are regulated by growth factors and the presence of bacteria. However, the molecular link connecting the diverse inputs that maintain CSC homeostasis remains largely unknown. We report that CSC proliferation is mediated by redox-dependent activation of epidermal growth factor receptor (EGFR) signaling via NADPH oxidase 1 (NOX1). NOX1 expression is CSC specific and is restricted to proliferative CSCs. In the absence of NOX1, CSCs fail to generate ROS and have a reduced proliferation rate. NOX1 expression is regulated by Toll-like receptor activation in response to the microbiota and serves to link CSC proliferati

SUBMITTER: van der Post S 

PROVIDER: S-EPMC10327654 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature