Intestinale mukosale Wundheilung im Rahmen entzündlicher Veränderungen im Gastrointestinaltrakt

• Applicant: Privatdozent Dr. Mike Laukötter
• Subject Area: General and Visceral Surgery
• Term: from 2006 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 23713201

The epithelial lining of the gastrointestinal (GI) tract forms a selectively permeable barrier regulating nutrient uptake while restricting luminal contents from underlying tissues. Mucosal wound resealing, in disorders such as Crohn`s Disease and Ulcerative Colitis, require both intestinal epithelial cell (IEC) proliferation and migration. Wnt signaling plays a critical role in regulating IEC proliferation. Dickkopf related protein-1 (DKK-1) is a Wnt signaling antagonist that has been shown to play a role in regulating wound healing in the GI tract. In our preliminary studies, we have established acute and chronic models of murine colitis and have characterized DKK-1 localization in mucosal tissues. Furthermore, using an in vitro cell model of the intestinal epithelial barrier, we have identified significant upregulation of DKK-1 expression upon induction of cell migration. The goal of this proposal is therefore to investigate the role of Dkk-1 in mucosal wound healing and cell migration. Utilizing acute and chronic models of experimental murine colitis, the expression and localization of Dkk-1 and its receptors will be characterized. We will also examine the effects of DKK-1 blockade on the inflammatory and wound healing responses. IECs cultured in two and three dimensions will be used to define the role of DKK-1 in cell migration and crypt regeneration using functional and biochemical techniques. The findings from these studies will aid in development of therapeutic strategies to promote wound closure in disorders of the intestinal tract.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Dr. Asma Nusrat