CLMP Expression is Increased in the Intestinal Epithelium Under Inflammatory Conditions and Regulates Intercellular Adhesion, Proliferation and Migration

Abstract

The intestine is lined by epithelial cells that form a dynamic physical barrier against external substances. Maintenance of this mucosal barrier requires proliferation, migration and differentiation of epithelial progenitor cells along the crypt‐luminal axis while keeping strong cell‐cell cohesion. Epithelial barrier function is created by tight junctions (TJ) and increased intestinal permeability has been linked with the pathogenesis of inflammatory bowel disease. CAR‐Like Membrane Protein (CLMP) is structurally related to the TJ transmembrane protein, Coxsackie and Adenovirus Receptor, but CLMP role in controlling intestinal epithelial barrier function in homeostasis and inflammation is not known. We observed that CLMP is distributed in intercellular junctions of murine and human intestinal epithelial cells (IECs), and its expression is increased after inflammatory cytokine exposure. CLMP overexpression in IECs, unlike its depletion, resulted in strengthened cell‐cell adhesion and increased cell migration after injury indicating a positive role of CLMP in the maintenance of epithelial barrier function and wound repair. Interestingly, CLMP overexpression led to decreased epithelial cell proliferation and inhibited the growth of subcutaneous xenografts in Rag1null mice. Our results support a role of CLMP in controlling intestinal epithelial barrier function and homeostasis. These studies will help to better understand signaling pathways that influence the intestinal epithelial barrier function during chronic inflammation.