Stromelysin-1-deficient fibroblasts display impaired contraction in vitro

Targeted disruption of the stromelysin-1 gene in mice causes a delay in exc isional wound healing due to a failure in wound contraction. Therefore, we postulated that stromelysin-1 activity is responsible for initiating contra ction. To test this hypothesis, we compared the contractile capacity of fib roblasts from stromelysin-1 knockout mice (strom-1 KO) with that of normal fibroblasts using a collagen gel contraction model. Fibroblast cultures wer e established from explants of skin and lung parenchyma from strom-1 KO and wild-type mice, then transferred to the surface of collagen gels. The exte nt of contraction was determined by measuring greatest gel diameter. Result s demonstrated that (1) all fibroblasts contracted collagen gels in a unifo rm concentric fashion, (2) skin fibroblasts from both sets of mice exhibite d greater gel contraction than did lung fibroblasts, and (3) strom-1 KO fib roblasts demonstrated significantly less contraction (21-23%) than wild-typ e fibroblasts. These data support the hypothesis that absence of stromelysi n-1 results in defective fibroblast contraction that may contribute to dela yed wound healing. (C) 1999 Academic Press.