Project Details
Projekt
Regulation of Intestinal Epithelial Wound closure by Wnt-ligands Wnt3/3a and Wnt5a.
Subject Area
General and Visceral Surgery
Term
from 2012 to 2013
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 223745117
Intestinal epithelial wounds, as seen in pathologic processes such as inflammatory bowel diseases, cause disruption of the mucosal barrier, which is associated with clinical symptoms such as diarrhea, rectal bleeding and pain. To rapidly cover injured surfaces, and re-establish the critical intestinal mucosal barrier, epithelial cells proliferate and migrate as a cohesive sheet. A broad spectrum of molecular processes is involved in this vital process.The large family of secreted Wnt proteins consists of highly conserved glycoproteins that play a role in embryonic development and stem cell homeostasis in the gut. However, the specific intestinal Wnt proteins that are elaborated following injury and inflammation, and the mechanisms by which they promote epithelial wound closure remain to be defined. Our preliminary results suggest that Wnt3/3a and Wnt5a are expressed in the intestinal mucosa and they promote intestinal epithelial wound closure. Thus, our objectives are to identify the mechanisms by which Wnt3/3a and Wnt5a regulate proliferation, migration and intestinal epithelial wound closure. We will accomplish these goals using complementary in vitro human epithelial cell cultures and in vivo approaches in murine models of intestinal wound closure. Understanding the basic mechanisms by which Wnt3/3a and Wnt5a modulate intestinal epithelial wound closure will not only advance our knowledge of epithelial barrier recovery in diseases such as inflammatory bowel diseases and recovery from surgical wounds, but will also aid in the development of new therapeutic strategies aimed at facilitating mucosal barrier recovery.
DFG Programme
Research Fellowships
International Connection
USA
