Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase.
BACKGROUND
Cell migration and adhesion are essential in intestinal epithelial wound healing and recovery from injury. Focal adhesion kinase (FAK) plays an important role in cell-extracellular matrix signal transduction. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes intestinal epithelial cell (IEC) migration and adhesion in vitro. The present study was designed to determine whether FAK is involved in HB-EGF-induced IEC migration and adhesion.


METHODS
A scrape wound healing model of rat IECs was used to examine the effect of HB-EGF on FAK-dependent cell migration in vitro. Immunofluorescence and Western blot analyses were performed to evaluate the effect of HB-EGF on the expression of phosphorylated FAK (p-FAK). Cell adhesion assays were performed to determine the role of FAK in HB-EGF-induced cell adhesion on fibronectin (FN).


RESULTS
HB-EGF significantly increased healing after scrape wounding, an effect that was reversed in the presence of an FAK inhibitor 14 (both with P < 0.05). HB-EGF increased p-FAK expression and induced p-FAK redistribution and actin reorganization in migrating rat IECs. Cell adhesion and spreading on FN were significantly increased by HB-EGF (P < 0.05). FAK inhibitor 14 significantly inhibited both intrinsic and HB-EGF-induced cell adhesion and spreading on FN (both with P < 0.05).


CONCLUSIONS
FAK phosphorylation and FAK-mediated signal transduction play essential roles in HB-EGF-mediated IEC migration and adhesion.
Department of Cardiovascular and Respiratory Medicine, Wuhan Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Pediatric Surgery, Nationwide Children's Hospital, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio. Electronic address: yanweisu@126.com.
Yanwei
Y
Su
Department of Pediatric Surgery, Nationwide Children's Hospital, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio. Electronic address: gail.besner@nationwidechildrens.org.
Gail E
GE
Besner
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells / Q000502:physiology*; D005353:Fibronectins; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D007413:Intestinal Mucosa / Q000201:enzymology*; D051381:Rats; D014945:Wound Healing
D005353:Fibronectins; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases
Cell adhesion; Cell migration; Focal adhesion kinase; HB-EGF; Wound healing