Crossref journal-article
American Society for Cell Biology (ASCB)
Molecular Biology of the Cell (1076)
Abstract

Thrombospondin 2 (TSP2)-null mice, generated by disruption of theThbs2 gene, display a variety of connective tissue abnormalities, including fragile skin and the presence of abnormally large collagen fibrils with irregular contours in skin and tendon. In this study we demonstrate that TSP2-null skin fibroblasts show a defect in attachment to a number of matrix proteins, and a reduction in cell spreading. To investigate the molecular mechanisms responsible for these abnormal cell–matrix interactions, we compared the levels of matrix metalloproteinases (MMPs) in wild-type and mutant fibroblasts. Isolation and analysis of gelatinases from conditioned media by gelatin-agarose affinity chromatography and gelatinolytic assays demonstrated that TSP2-null fibroblasts produce a 2-fold increase in gelatinase A (MMP2) compared with wild-type cells. The adhesive defect was corrected by treatment of TSP2-null fibroblasts with soluble TSP2, with the MMP inhibitors BB94 and tissue inhibitor of metalloproteinase-2, and with a neutralizing antibody to MMP2. Moreover, stable transfection of TSP2-null fibroblasts with mouse TSP2 cDNA corrected both the adhesive defect and the altered expression of MMP2. Finally, MMP2 was shown to interact with TSP2 in a direct-binding plate assay. We conclude that TSP2 plays an important role in cell–matrix interactions, and that a deficiency in the protein results in increased levels of MMP2 that contribute to the adhesive defect in TSP2-null fibroblasts and could play a role in the complex phenotype of TSP2-null mice.

Bibliography

Yang, Z., Kyriakides, T. R., & Bornstein, P. (2000). 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. Molecular Biology of the Cell, 11(10), 3353–3364.

Authors 3
  1. Zhantao Yang (first)
  2. Themis R. Kyriakides (additional)
  3. Paul Bornstein (additional)
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Dates
Type When
Created 12 years, 2 months ago (July 2, 2013, 7:41 p.m.)
Deposited 3 years, 6 months ago (Feb. 26, 2022, 9:40 p.m.)
Indexed 1 week, 3 days ago (Aug. 27, 2025, 12:18 p.m.)
Issued 24 years, 11 months ago (Oct. 1, 2000)
Published 24 years, 11 months ago (Oct. 1, 2000)
Published Print 24 years, 11 months ago (Oct. 1, 2000)
Funders 0

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@article{Yang_2000, title={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}, volume={11}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.11.10.3353}, DOI={10.1091/mbc.11.10.3353}, number={10}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Yang, Zhantao and Kyriakides, Themis R. and Bornstein, Paul}, editor={Hynes, Richard}, year={2000}, month=oct, pages={3353–3364} }