title: 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.
authors.affiliation: Department of Pediatric Surgery, Nationwide Children's Hospital, The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Su
authors.forename: Jixin
authors.initials: J
authors.lastname: Yang
authors.forename: Gail E
authors.initials: GE
authors.lastname: Besner
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D066257:Heparin-binding EGF-like Growth Factor; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism*; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D039482:Integrin alpha5; D039641:Integrin beta Chains; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin; D066246:ErbB Receptors