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 CellâMatrix 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), 3353â3364.
References
43
Referenced
151
10.1074/jbc.274.42.30087
/ J. Biol. Chem. by Barmina O.Y. (1999){'key': 'B4', 'first-page': '73a', 'volume': '10', 'author': 'Bein K.', 'year': '1999', 'journal-title': 'Mol. Biol. Cell'}
/ Mol. Biol. Cell by Bein K. (1999)10.1093/carcin/17.9.1805
/ Carcinogenesis by Bian J. (1996)10.1083/jcb.103.1.231
/ J. Cell Biol. by Birk D.E. (1986)10.1083/jcb.130.3.503
/ J. Cell Biol. by Bornstein P. (1995)10.1016/0076-6879(94)45006-4
/ Methods Enzymol. by Bornstein P. (1994)10.1083/jcb.147.3.619
/ J. Cell Biol. by Carragher N.O. (1999)10.1016/S0003-2697(79)80017-2
/ Anal. Biochem. by Cawston T.E. (1979)10.1016/S0021-9258(18)31625-9
/ J. Biol. Chem. by Chen H. (1994)10.1074/jbc.271.27.15993
/ J. Biol. Chem. by Chen H. (1996)10.1016/0003-2697(87)90021-2
/ Anal. Biochem. by Chomczynski P. (1987)10.1016/S0021-9258(18)68680-6
/ J. Biol. Chem. by Collier I.E. (1988)10.1016/S0092-8674(00)81460-9
/ Cell by Crawford S.E. (1998)10.1093/emboj/17.7.1860
/ EMBO J. by Gilmour D.T. (1998)10.1074/jbc.273.6.3604
/ J. Biol. Chem. by Haas T.L. (1998)10.1055/s-0038-1648962
/ Thromb. Haemostasis by Hogg P.J. (1994){'key': 'B20', 'first-page': '1048', 'volume': '58', 'author': 'Itoh T.', 'year': '1998', 'journal-title': 'Cancer Res.'}
/ Cancer Res. by Itoh T. (1998)10.1073/pnas.88.12.5096
/ Proc. Natl. Acad. Sci. USA by Jat P.S. (1991)10.1073/pnas.96.8.4449
/ Proc. Natl. Acad. Sci. USA by Kyriakides T.R. (1999)10.1046/j.1523-1747.1999.00755.x
/ J. Invest. Dermatol. by Kyriakides T.R. (1999)10.1083/jcb.140.2.419
/ J. Cell Biol. by Kyriakides T.R. (1998)10.1177/002215549804600904
/ J. Histochem. Cytochem. by Kyriakides T.R. (1998)10.1111/1523-1747.ep12384118
/ J. Invest. Dermatol. by Lafuma C. (1994)10.1172/JCI1684
/ J. Clin. Invest. by Lawler J. (1998)10.1242/jcs.111.3.347
/ J. Cell Sci. by Levenberg S. (1998){'key': 'B29', 'first-page': '2824', 'volume': '5', 'author': 'Miyake H.', 'year': '1999', 'journal-title': 'Clin. Cancer Res.'}
/ Clin. Cancer Res. by Miyake H. (1999)10.1083/jcb.137.7.1663
/ J. Cell Biol. by Monier-Gavelle F. (1997)10.1002/jcp.1041570219
/ J. Cell Physiol. by Murphy A.N. (1993)10.1016/S0021-9258(19)74381-6
/ J. Biol. Chem. by Murphy-Ullrich J.E. (1993){'key': 'B33', 'first-page': '2674', 'volume': '39', 'author': 'Norose K.', 'year': '1998', 'journal-title': 'Invest. Ophthalmol. Vis. Sci.'}
/ Invest. Ophthalmol. Vis. Sci. by Norose K. (1998)10.1074/jbc.274.41.29568
/ J. Biol. Chem. by O'Reilly M.S. (1999)10.1016/S0022-2143(97)90141-4
/ J. Lab. Clin. Med. by Panetti T.S. (1997)10.1016/0303-7207(94)90201-1
/ Mol. Cell. Endocrinol. by Pellerin S. (1994)10.1016/1047-8477(91)90064-4
/ J. Struct. Biol. by Ploetz C. (1991)10.1002/j.1460-2075.1995.tb07072.x
/ EMBO J. by Ray J.M. (1995)10.1016/S0021-9258(19)62724-9
/ J. Biol. Chem. by Sage H. (1986)10.1016/S0021-9258(18)98545-5
/ J. Biol. Chem. by Sage E.H. (1991)10.1073/pnas.96.26.14888
/ Proc. Natl. Acad. Sci. USA by Streit M. (1999)10.1096/fasebj.9.10.7615159
/ FASEB. J. by Strickland D.K. (1995)10.1073/pnas.76.9.4350
/ Proc. Natl. Acad. Sci. USA by Towbin H. (1979)10.1006/bbrc.1995.2780
/ Biochem. Biophys. Res. Commun. by Volpert O.V. (1995)10.1016/S0092-8674(00)81169-1
/ Cell by Vu T.H. (1998)10.1111/j.1699-0463.1999.tb01521.x
/ Apmis by Werb Z. (1999)
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) |
@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} }