Matricellular proteins as modulators of cell-matrix interactions: adhesive defect in thrombospondin 2-null fibroblasts is a consequence of increased levels of matrix metalloproteinase-2.

摘要: Thrombospondin 2 (TSP2)-null mice, generated by disruption of the Thbs2 gene, display a variety connective tissue abnormalities, including fragile skin and presence abnormally large collagen fibrils with irregular contours in tendon. In this study we demonstrate that TSP2-null fibroblasts show defect attachment to number matrix proteins, reduction cell spreading. To investigate molecular mechanisms responsible for these abnormal cell–matrix interactions, compared levels metalloproteinases (MMPs) wild-type mutant fibroblasts. Isolation analysis gelatinases from conditioned media gelatin-agarose affinity chromatography gelatinolytic assays demonstrated produce 2-fold increase gelatinase A (MMP2) cells. The adhesive was corrected treatment soluble TSP2, MMP inhibitors BB94 inhibitor metalloproteinase-2, neutralizing antibody MMP2. Moreover, stable transfection mouse TSP2 cDNA both altered expression Finally, MMP2 shown interact direct-binding plate assay. We conclude plays an important role deficiency protein results increased contribute could play complex phenotype mice.