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1 Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA
* To whom correspondence should be addressed. E-mail: denise_hocking{at}urmc.rochester.edu.
The continuous conversion of soluble fibronectin into extracellular matrix fibrils occurs through a dynamic, cell-dependent process. As the extracellular matrix is assembled, changes in the conformation of matrix proteins may expose biologically active, matricryptic sites that alter cell behavior. In this study, an in vitro model of wound healing was used to determine the role of matrix fibronectin in airway epithelial cell motility. Our findings indicate that under basal conditions, small airway epithelial cell (SAEC) migration requires active fibronectin matrix polymerization. Furthermore, SAEC migration is significantly increased by the interaction of cells with a recombinant construct containing fibronectin's matricryptic III-1 site. In contrast, addition of increasing amounts of fibronectin to SAECs significantly decreased the rate of cell migration. This fibronectin-induced inhibition of cell migration was overcome by blocking excess fibronectin matrix deposition. These data indicate that small airway epithelial cell migration is regulated in a biphasic manner by the polymerization of fibronectin into the extracellular matrix and suggest a stimulatory role for fibronectin's matricryptic III-1 site in cell motility.
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