![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 11, Issue 10, 3353-3364, October 2000
Departments of *Biochemistry and Thrombospondin 2 (TSP2)-null mice, generated by disruption of the
Thbs2 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.
Medicine, University
of Washington, Seattle, Washington 98195
Corresponding author: E-mail
address: bornsten{at}u.washington.edu.
This article has been cited by other articles:
|
|
 |
|
  S. MacLauchlan, E. A. Skokos, A. Agah, J. Zeng, W. Tian, J. M. Davidson, P. Bornstein, and T. R. Kyriakides Enhanced Angiogenesis and Reduced Contraction in Thrombospondin-2-null Wounds Is Associated With Increased Levels of Matrix Metalloproteinases-2 and -9, and Soluble VEGF J. Histochem. Cytochem., April 1, 2009; 57(4): 301 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. MacLauchlan, E. A. Skokos, N. Meznarich, D. H. Zhu, S. Raoof, J. M. Shipley, R. M. Senior, P. Bornstein, and T. R. Kyriakides Macrophage fusion, giant cell formation, and the foreign body response require matrix metalloproteinase 9 J. Leukoc. Biol., April 1, 2009; 85(4): 617 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tang, E. A. Scheef, S. Wang, C. M. Sorenson, C. B. Marcus, C. R. Jefcoate, and N. Sheibani CYP1B1 expression promotes the proangiogenic phenotype of endothelium through decreased intracellular oxidative stress and thrombospondin-2 expression Blood, January 15, 2009; 113(3): 744 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Krady, J. Zeng, J. Yu, S. MacLauchlan, E. A. Skokos, W. Tian, P. Bornstein, W. C. Sessa, and T. R. Kyriakides Thrombospondin-2 Modulates Extracellular Matrix Remodeling during Physiological Angiogenesis Am. J. Pathol., September 1, 2008; 173(3): 879 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Lillis, L. B. Van Duyn, J. E. Murphy-Ullrich, and D. K. Strickland LDL Receptor-Related Protein 1: Unique Tissue-Specific Functions Revealed by Selective Gene Knockout Studies Physiol Rev, July 1, 2008; 88(3): 887 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Behera, L. Feng, B. Yonish, W. Catherino, S.-H. Jung, and P. C. Leppert Thrombospondin-1 and Thrombospondin-2 mRNA and TSP-1 and TSP-2 Protein Expression in Uterine Fibroids and Correlation to the Genes COL1A1 and COL3A1 and to the Collagen Cross-link Hydroxyproline Reproductive Sciences, December 1, 2007; 14(8_suppl): 63 - 76. [Abstract] [PDF]
|
|
|
|
|
|
F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. I. Stenina, E. J. Topol, and E. F. Plow Thrombospondins, Their Polymorphisms, and Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1886 - 1894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Behbod, W. Xian, C. A. Shaw, S. G. Hilsenbeck, A. Tsimelzon, and J. M. Rosen Transcriptional Profiling of Mammary Gland Side Population Cells Stem Cells, April 1, 2006; 24(4): 1065 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Deschamps and F. G. Spinale Pathways of matrix metalloproteinase induction in heart failure: Bioactive molecules and transcriptional regulation Cardiovasc Res, February 15, 2006; 69(3): 666 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Barker, G. Baneyx, M. Cardo-Vila, G. A. Workman, M. Weaver, P. M. Menon, S. Dedhar, S. A. Rempel, W. Arap, R. Pasqualini, et al. SPARC Regulates Extracellular Matrix Organization through Its Modulation of Integrin-linked Kinase Activity J. Biol. Chem., October 28, 2005; 280(43): 36483 - 36493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Y. Fears, J. R. Grammer, J. E. Stewart Jr., D. S. Annis, D. F. Mosher, P. Bornstein, and C. L. Gladson Low-Density Lipoprotein Receptor-Related Protein Contributes to the Antiangiogenic Activity of Thrombospondin-2 in a Murine Glioma Model Cancer Res., October 15, 2005; 65(20): 9338 - 9346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Agah, T. R. Kyriakides, and P. Bornstein Proteolysis of Cell-Surface Tissue Transglutaminase by Matrix Metalloproteinase-2 Contributes to the Adhesive Defect and Matrix Abnormalities in Thrombospondin-2-Null Fibroblasts and Mice Am. J. Pathol., July 1, 2005; 167(1): 81 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Puolakkainen, A. D. Bradshaw, R. A. Brekken, M. J. Reed, T. Kyriakides, S. E. Funk, M. D. Gooden, R. B. Vernon, T. N. Wight, P. Bornstein, et al. SPARC-thrombospondin-2-double-null Mice Exhibit Enhanced Cutaneous Wound Healing and Increased Fibrovascular Invasion of Subcutaneous Polyvinyl Alcohol Sponges J. Histochem. Cytochem., May 1, 2005; 53(5): 571 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Emonard, G. Bellon, L. Troeberg, A. Berton, A. Robinet, P. Henriet, E. Marbaix, K. Kirkegaard, L. Patthy, Y. Eeckhout, et al. Low Density Lipoprotein Receptor-related Protein Mediates Endocytic Clearance of Pro-MMP-2{middle dot}TIMP-2 Complex through a Thrombospondin-independent Mechanism J. Biol. Chem., December 24, 2004; 279(52): 54944 - 54951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W.M. Schellings, Y. M. Pinto, and S. Heymans Matricellular proteins in the heart: possible role during stress and remodeling Cardiovasc Res, October 1, 2004; 64(1): 24 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Spinale Cell-Matrix Signaling and Thrombospondin: Another Link to Myocardial Matrix Remodeling Circ. Res., September 3, 2004; 95(5): 446 - 448. [Full Text] [PDF]
|
|
|
|
|
|
B. Schroen, S. Heymans, U. Sharma, W. M. Blankesteijn, S. Pokharel, J. P.M. Cleutjens, J. G. Porter, C. T.A. Evelo, R. Duisters, R. E.W. van Leeuwen, et al. Thrombospondin-2 Is Essential for Myocardial Matrix Integrity: Increased Expression Identifies Failure-Prone Cardiac Hypertrophy Circ. Res., September 3, 2004; 95(5): 515 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kokenyesi, L. C. Armstrong, A. Agah, R. Artal, and P. Bornstein Thrombospondin 2 Deficiency in Pregnant Mice Results in Premature Softening of the Uterine Cervix Biol Reprod, February 1, 2004; 70(2): 385 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Omer, J. B. de Souza, P. H. Corran, A. A. Sultan, and E. M. Riley Activation of Transforming Growth Factor {beta} by Malaria Parasite-derived Metalloproteinases and a Thrombospondin-like Molecule J. Exp. Med., December 15, 2003; 198(12): 1817 - 1827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Kyriakides, P. Rojnuckarin, M. A. Reidy, K. D. Hankenson, T. Papayannopoulou, K. Kaushansky, and P. Bornstein Megakaryocytes require thrombospondin-2 for normal platelet formation and function Blood, May 15, 2003; 101(10): 3915 - 3923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hamsten and P. Eriksson Thrombospondins and Premature Coronary Artery Disease: Time to Go Beyond Genotype-Phenotype Association Studies Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 6 - 7. [Full Text] [PDF]
|
|
|
|
|
|
S. M. Boekholdt, M. D. Trip, R. J.G. Peters, M. Engelen, J. M.A. Boer, E. J.M. Feskens, A. H. Zwinderman, J. J.P. Kastelein, and P. H. Reitsma Thrombospondin-2 Polymorphism Is Associated With a Reduced Risk of Premature Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22 (12): e24 - e27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Agah, T. R. Kyriakides, J. Lawler, and P. Bornstein The Lack of Thrombospondin-1 (TSP1) Dictates the Course of Wound Healing in Double-TSP1/TSP2-Null Mice Am. J. Pathol., September 1, 2002; 161(3): 831 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Armstrong, B. Bjorkblom, K. D. Hankenson, A. W. Siadak, C. E. Stiles, and P. Bornstein Thrombospondin 2 Inhibits Microvascular Endothelial Cell Proliferation by a Caspase-independent Mechanism Mol. Biol. Cell, June 1, 2002; 13(6): 1893 - 1905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.O. HYNES, J.C. LIVELY, J.H. MCCARTY, D. TAVERNA, S.E. FRANCIS, K. HODIVALA-DILKE, and Q. XIAO The Diverse Roles of Integrins and Their Ligands in Angiogenesis Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 143 - 154. [Abstract] [PDF]
|
|
|
|
|
|
C.-C. Chen, F.-E Mo, and L. F. Lau The Angiogenic Factor Cyr61 Activates a Genetic Program for Wound Healing in Human Skin Fibroblasts J. Biol. Chem., December 7, 2001; 276(50): 47329 - 47337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Weeks, W. He, K. L. Olson, and X.-J. Wang Inducible Expression of Transforming Growth Factor {beta}1 in Papillomas Causes Rapid Metastasis Cancer Res., October 1, 2001; 61(20): 7435 - 7443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Kyriakides, Y.-H. Zhu, Z. Yang, G. Huynh, and P. Bornstein Altered Extracellular Matrix Remodeling and Angiogenesis in Sponge Granulomas of Thrombospondin 2-Null Mice Am. J. Pathol., October 1, 2001; 159(4): 1255 - 1262. [Abstract] [Full Text]
|
|
|
|
|
|
Z. Yang, D. K. Strickland, and P. Bornstein Extracellular Matrix Metalloproteinase 2 Levels Are Regulated by the Low Density Lipoprotein-related Scavenger Receptor and Thrombospondin 2 J. Biol. Chem., March 9, 2001; 276(11): 8403 - 8408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hahn-Dantona, J. F. Ruiz, P. Bornstein, and D. K. Strickland The Low Density Lipoprotein Receptor-related Protein Modulates Levels of Matrix Metalloproteinase 9 (MMP-9) by Mediating Its Cellular Catabolism J. Biol. Chem., April 27, 2001; 276(18): 15498 - 15503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bornstein, V. Walsh, J. Tullis, E. Stainbrook, J. F. Bateman, and S. G. Hormuzdi The Globular Domain of the Proalpha 1(I) N-Propeptide Is Not Required for Secretion, Processing by Procollagen N-Proteinase, or Fibrillogenesis of Type I Collagen in Mice J. Biol. Chem., January 18, 2002; 277(4): 2605 - 2613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Topol, J. McCarthy, S. Gabriel, D. J. Moliterno, W. J. Rogers, L. K. Newby, M. Freedman, J. Metivier, R. Cannata, C. J. O'Donnell, et al. Single Nucleotide Polymorphisms in Multiple Novel Thrombospondin Genes May Be Associated With Familial Premature Myocardial Infarction Circulation, November 27, 2001; 104(22): 2641 - 2644. [Abstract] [Full Text] [PDF]
|
|
