Cell differentiation in the murine intestine requires NADPH oxidase 1

Abstract

It is increasingly documented that cells deliberately generate of reactive oxygen species (ROS) to function as signaling intermediates in the control cell proliferation. These comprise of regulatory networks that regulate progenitor cell differentiation in the murine intestine. However, how ROS mediates these responses remain to be fully defined. Recent reports have shown that the ROS‐generating enzyme NADPH oxidase 1 (Nox1) is highly expressed by colon epithelia. Indeed, a recent report identified Nox1 as a novel IBD susceptibility gene where mutations in Nox1 was discovered in patients presenting with severe pancolitis. Here, we report that ROS generation by Nox1 in the murine colon is necessary for normal intestinal stem cell proliferation and differentiation. Gut epithelial‐specific Nox1‐null mice exhibited increased gut permeability, skewed differentiation, and slowed recovery rates following gut injury. Together, these results implicate Nox1 as an essential protein in epithelial cell homeostasis and response to injury, and reveal a novel mechanism for the maintenance of intestinal tissue structure.