Fibronectin matrix polymerization regulates small airway epithelial cell migration

Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642 Submitted 31 October 2002 ; accepted in final form 6 March 2003 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 increased significantly 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 SAEC migration is regulated in a biphasic manner by the polymerization of fibronectin in the extracellular matrix and suggest a stimulatory role for fibronectin's matricryptic III-1 site in cell motility. extracellular matrix; wound healing; cell motility; lung repair Address for reprint requests and other correspondence: D. C. Hocking, Dept. of Pharmacology and Physiology, Univ. of Rochester Medical Center, 601 Elmwood Ave., Box 711, Rochester, NY 14642 (E-mail: denise_hocking{at}urmc.rochester.edu ).