Role of matrilysin-mediated E-cadherin shedding in wound healing. Tissue injury leads to proliferation, differentiation, and migration of epithelial cells. These processes involve the coordinated action of various proteins, including several matrix metalloproteinases (MMPs). Previous data from our lab demonstrated that matrilysin (MMP-7) is required for repair of wounds to the lung. Matrilysin is expressed on basolateral surfaces of migrating airway epithelial cells, and it mediates E- cadherin shedding during the re-epithelialization process. In the absence of matrilysin, E-cadherin is not shed from wound edge cells in response to injury, and airway wounds do not close. We will test the hypothesis that matrilysin shedding of E-cadherin promotes epithelial-to-mesenchymal transformation and re-epithelialialization in mouse lungs.
Aim1 is to identify the matrilysin cleavage site in mouse E-cadherin and to develop a proteolytic-resistant E-cadherin construct in an epithelial cell culture model.
Aim 2 is to analyze the effect of E-cadherin shedding in vivo by developing a transgenic mouse line expressing a proteolytic-resistant E-cadherin on an E-cadherin-null background. The experiments proposed here will determine the function of matrilysin-mediated E-cadherin shedding in wound repair. ? ? ?
| Ra, Hyun-Jeong; Harju-Baker, Susanna; Zhang, Fuming et al. (2009) Control of promatrilysin (MMP7) activation and substrate-specific activity by sulfated glycosaminoglycans. J Biol Chem 284:27924-32 |
