HB-EGF promotes intestinal restitution by affecting integrin–extracellular matrix interactions and intercellular adhesions

Abstract

Restitution is a critical form of intestinal epithelial cell (IEC) healing. We have previously shown that heparin-binding epidermal-like growth factor (HB-EGF) is necessary for IEC restitution; however, the mechanisms by which HB-EGF promotes restitution remain poorly understood. This study was designed to investigate whether HB-EGF promotes intestinal restitution by affecting integrin–extracellular matrix (ECM) interactions and intercellular adhesions. The effect of HB-EGF administration was examined in a murine necrotizing enterocolitis (NEC) model in vivo and an IEC line scrape-wound healing model in vitro. We evaluated the effect of HB-EGF on the expression of integrins, E-cadherin/β-catenin, and integrin α5β1-dependent cell–ECM interactions. We found that HB-EGF promoted intestinal restitution and the expression of integrin α5β1. HB-EGF promoted integrin α5β1-dependent cell adhesion and spreading. In addition, HB-EGF decreased the expression E-cadherin/β-catenin, via the activation of v-erb-b2 erythroblastic leukemia viral oncogene homolog (ErbB-1). We conclude that HB-EGF promotes intestinal restitution by affecting integrin–ECM interactions and intercellular adhesions.