Ohio State Navbar

The Ohio State UniversityOffice of International Affairs

give a donation

Heparin-binding EGF-like growth factor (HB-EGF) promotes intestinal epithelial cell migration by enhancing epithelial cell-matrix (ECM) interactions

Research Scholar

Yanwei Su , Children's Hospital - Pediatrics (China)
Gail E Besner, Faculty Mentor

Biography

Yanwei Su received her medical degree from Tongji Medical College of Huazhong University of Science and Technology in 2009. After graduation, she began her residency training in the Department of Cardiovascular Diseases in Pu'ai Hospital of Wuhan, China. Su was accepted as a J-1 international scholar by Dr. Gail Besner at Nationwide Children's Hospital in May 2011. Her work focuses on the mechanisms by which HB-EGF promotes intestinal restitution, specifically examining epithelial cell-matrix (ECM) interactions in cultured rat intestinal epithelial cells.

What is the issue or problem addressed in your research?

Restitution, a critical form of intestinal epithelial cell (IEC) healing, is the first step in mucosal repair. We have previously shown that HB-EGF is necessary for intrinsic IEC restitution in vitro. However, the mechanisms by which HB-EGF improves intestinal restitution remain poorly understood. This study was designed to investigate whether HB-EGF promotes intestinal restitution in vitro by affecting integrin function and mediators of restitution.

What methodology did you use in your research?

Rat intestinal epithelial (RIE-1) cells were cultured in vitro and subjected to scrape injury or unscraped controls. After scraping, cells receive either HB-EGF (10ng/ml), EGFR blockade with AG1478 (500nmol/L), or AG1478 followed 30 minutes later by HB-EGF. Non-treated cells served as negative controls. Cell migration was quantified 18h later. Cells were fixed for immunocytochemistry or were harvested for Western blotting for integrin subunits and restitution mediators (FAK, paxillin, RhoA, Rac/Cdc42).

What are the purpose/rationale and implications of your research?

Cell migration was significantly increased in cells that received HB-EGF (p<0.05), and was significantly decreased in cells that received AG1478 + HB-EGF. Immunocytochemistry demonstrated that the expression of integrin subunits α3, α5 and β1 was increased in cells at the migrating wound edges. Addition of HB-EGF significantly increased the levels of integrin subunits α5 and β1, whereas addition of AG1478 + HB-EGF decreased the expression of these subunits. There were no significant differences in protein levels of integrin subunits or in phosphorylation levels of FAK, paxillin or Rac/Cdc42 between scraped and unscraped cells, however, phosphorylated RhoA significantly increased after scraping (p<0.05). Addition of HB-EGF to both unscraped and scraped cells significantly increased the levels of integrin subunits α5 and β1, and increased phosphorylation of FAK, paxillin, RhoA and Rac/Cdc42 (all with p<0.05). Addition of AG1478 + HB-EGF significantly decreased the levels of these mediators compared with cells that received HB-EGF only (all with p<0.05). We conclude that HB-EGF is an important reagent for wound healing of intestinal epithelial cells by enhancing epithelial cell-matrix (ECM) interactions.