Up-regulation of thrombospondin-2 in Akt1-null mice contributes to compromised tissue repair due to abnormalities in fibroblast function

Journal of Biological Chemistry

Volumn 290, Issue 1, 2015, Pages 409-422

  Bancroft, Tara ^a   Bouaouina, Mohamed ^a   Roberts, Sophia ^a   Lee, Monica ^a   Calderwood, David A ^a   Schwartz, Martin ^a   Simons, Michael ^a   Sessa, William C ^a   Kyriakides, Themis R ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADHESION; CELL CULTURE; CHEMICAL ACTIVATION; FIBROBLASTS; MAMMALS; MORPHOLOGY; TISSUE;

CELL MORPHOLOGY; CONSTITUTIVELY ACTIVES; MIGRATION RATES; MULTIPLE FACTORS; SURFACE EXPRESSION; THROMBOSPONDIN; TISSUE REPAIR; VASCULAR REMODELING;

REPAIR;

AKT 1 PROTEIN; BETA1 INTEGRIN; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FIBRONECTIN; PROTEIN GLUTAMINE GAMMA GLUTAMYLTRANSFERASE 2; PROTEIN KINASE B; RAC PROTEIN; THROMBOSPONDIN 2; UNCLASSIFIED DRUG; AKT1 PROTEIN, MOUSE; AKT2 PROTEIN, MOUSE; NEUROPEPTIDE; NOS3 PROTEIN, MOUSE; RAC1 PROTEIN; RAC1 PROTEIN, MOUSE; SMALL INTERFERING RNA; THROMBOSPONDIN;

ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL ADHESION; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; INTRACELLULAR SIGNALING; KNOCKOUT MOUSE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; SKIN FIBROBLAST; TISSUE REPAIR; UPREGULATION; WOUND HEALING; ANIMAL; ANTAGONISTS AND INHIBITORS; BLUNT TRAUMA; CELL MOTION; DEFICIENCY; FIBROBLAST; GENE EXPRESSION REGULATION; GENETIC COMPLEMENTATION; GENETICS; INJURIES; METABOLISM; PATHOLOGY; PRIMARY CELL CULTURE; SIGNAL TRANSDUCTION; SKIN;

MUS;

ANIMALS; ANTIGENS, CD29; CELL MOVEMENT; FIBROBLASTS; GENE EXPRESSION REGULATION; GENETIC COMPLEMENTATION TEST; MICE; MICE, KNOCKOUT; NEUROPEPTIDES; NITRIC OXIDE SYNTHASE TYPE III; PRIMARY CELL CULTURE; PROTO-ONCOGENE PROTEINS C-AKT; RAC1 GTP-BINDING PROTEIN; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; SKIN; THROMBOSPONDINS; WOUND HEALING; WOUNDS, NONPENETRATING;

EID: 84920659108     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.618421     Document Type: Article

References (71)

1. Folkman, J. (2003) Fundamental concepts of the angiogenic process. Curr. Mol. Med. 3, 643-651
2. Folkman, J., and Klagsbrun, M. (1987) Angiogenic factors. Science 235, 442-447
3. Skaletz-Rorowski, A., Kureishi, Y., Shiojima, I., and Walsh, K. (2004) The pro- and antiangiogenic effects of statins. Semin. Vasc. Med. 4, 395-400
4. Adya, R., Tan, B. K., Chen, J., and Randeva, H. S. (2012) Protective actions of globular and full-length adiponectin on human endothelial cells: novel insights into adiponectin-induced angiogenesis. J. Vasc. Res. 49, 534-543
5. Zachary, I., and Gliki, G. (2001) Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc. Res. 49, 568-581
6. Sessa, W. C. (2009) Molecular control of blood flow and angiogenesis: role of nitric oxide. J. Thromb. Haemost. 7, 35-37
7. Suárez, Y., and Sessa, W. C. (2009) MicroRNAs as novel regulators of angiogenesis. Circ. Res. 104, 442-454
8. Carmeliet, P., and Jain, R. K. (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298-307
9. Kyriakides, T. R., Zhu, Y. H., Yang, Z., and Bornstein, P. (1998) The distribution of the matricellular protein thrombospondin 2 in tissues of embryonic and adult mice. J. Histochem. Cytochem. 46, 1007-1015
10. MacLauchlan, S., Yu, J., Parrish, M., Asoulin, T. A., Schleicher, M., Krady, M. M., Zeng, J., Huang, P. L., Sessa, W. C., and Kyriakides, T. R. (2011) Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2. Proc. Natl. Acad. Sci. U.S.A. 108, E1137-E1145
11. Ackah, E., Yu, J., Zoellner, S., Iwakiri, Y., Skurk, C., Shibata, R., Ouchi, N., Easton, R. M., Galasso, G., Birnbaum, M. J., Walsh, K., and Sessa, W. C. (2005) Akt1/protein kinase Bα is critical for ischemic and VEGF-mediated angiogenesis. J. Clin. Invest. 115, 2119-2127
12. Chen, J., Somanath, P. R., Razorenova, O., Chen, W. S., Hay, N., Bornstein, P., and Byzova, T. V. (2005) Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo. Nat. Med. 11, 1188-1196
13. Bornstein, P. (2009) Thrombospondins function as regulators of angiogenesis. J Cell Commun. Signal. 3, 189-200
14. Armstrong, L. C., and Bornstein P. (2003) Thrombospondins 1 and 2 function as inhibitors of angiogenesis. Matrix Biol. 22, 63-71
15. Bornstein, P. (1992) Thrombospondins: structure and regulation of expression. FASEB J. 6, 3290-3299
16. Bornstein, P. (2001) Thrombospondins as matricellular modulators of cell function. J. Clin. Invest. 107, 929-934
17. Bornstein, P., Agah, A., and Kyriakides, T. R. (2004) The role of thrombospondins 1 and 2 in the regulation of cell-matrix interactions, collagen fibril formation, and the response to injury. Int. J. Biochem. Cell Biol. 36, 1115-1125
18. Krady, M. M., Zeng, J., Yu, J., MacLauchlan, S., Skokos, E. A., Tian, W., Bornstein, P., Sessa, W. C., and Kyriakides, T. R. (2008) Thrombospondin-2 modulates extracellular matrix remodeling during physiological angiogenesis. Am. J. Pathol. 173, 879-891
19. Kyriakides, T. R., Tam, J. W., and Bornstein, P. (1999) Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene. J. Invest. Dermatol. 113, 782-787
20. Agah, A., Kyriakides, T. R., Letrondo, N., Björkblom, B., and Bornstein, P. (2004) Thrombospondin 2 levels are increased in aged mice: consequences for cutaneous wound healing and angiogenesis. Matrix Biol. 22, 539-547
21. Maclauchlan, S., Skokos, E. A., Agah, A., Zeng, J., Tian, W., Davidson, J. M., Bornstein, P., and Kyriakides, T. R. (2009) 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. 57, 301-313
22. Kyriakides, T. R., Zhu, Y. H., Yang, Z., Huynh, G., and Bornstein, P. (2001) Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of thrombospondin 2-null mice. Am. J. Pathol. 159, 1255-1262
23. Kyriakides, T. R., Leach, K. J., Hoffman, A. S., Ratner, B. D., and Bornstein, P. (1999) Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity. Proc. Natl. Acad. Sci. U.S.A. 96, 4449-4454
24. Simantov, R., Febbraio, M., and Silverstein, R. L. (2005) The antiangiogenic effect of thrombospondin-2 is mediated by CD36 and modulated by histidine-rich glycoprotein. Matrix Biol. 24, 27-34
25. Isenberg, J. S., Annis, D. S., Pendrak, M. L., Ptaszynska, M., Frazier, W. A., Mosher, D. F., and Roberts, D. D. (2009) Differential interactions of thrombospondin-1, -2, and -4 with CD47 and effects on cGMP signaling and ischemic injury responses. J. Biol. Chem. 284, 1116-1125
26. Kyriakides, T. R., Zhu, Y. H., Smith, L. T., Bain, S. D., Yang, Z., Lin, M. T., Danielson, K. G., Iozzo, R. V., LaMarca, M., McKinney, C. E., Ginns, E. I., and Bornstein, P. (1998) Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis. J. Cell Biol. 140, 419-430
27. Somanath, P. R., and Byzova, T. V., (2009) 14-3-3β-Rac1-p21 activated kinase signaling regulates Akt1-mediated cytoskeletal organization, lamellipodia formation and fibronectin matrix assembly. J. Cell Physiol. 218, 394-404
28. Kimura, K., Kawamoto, K., Teranishi, S., and Nishida, T. (2006) Role of Rac1 in fibronectin-induced adhesion and motility of human corneal epithelial cells. Invest. Ophthalmol. Vis. Sci. 47, 4323-4329
29. Wennerberg, K., Ellerbroek, S. M., Liu, R. Y., Karnoub, A. E., Burridge, K., and Der, C. J. (2002) RhoG signals in parallel with Rac1 and Cdc42. J. Biol. Chem. 277, 47810-47817
30. Wheeler, A. P., Wells, C. M., Smith, S. D., Vega, F. M., Henderson, R. B., Tybulewicz, V. L., and Ridley, A. J. (2006) Rac1 and Rac2 regulate macrophage morphology but are not essential for migration. J. Cell Sci. 119, 2749-2757
31. Cernuda-Morollón, E., and Ridley, A. J. (2006) Rho GTPases and leukocyte adhesion receptor expression and function in endothelial cells. Circ. Res. 98, 757-767
32. Zhou, G. L., Tucker, D. F., Bae, S. S., Bhatheja, K., Birnbaum, M. J., and Field, J. (2006) Opposing roles for Akt1 and Akt2 in Rac/Pak signaling and cell migration. J. Biol. Chem. 281, 36443-36453
33. Somanath, P. R., Kandel, E. S., Hay, N., and Byzova, T. V. (2007) Akt1 signaling regulates integrin activation, matrix recognition, and fibronectin assembly. J. Biol. Chem. 282, 22964-22976
34. 3 regulates cell adhesion and migration to bone sialoprotein. Exp. Cell Res. 254, 299-308
35. Plow, E. F., Haas, T. A., Zhang, L., Loftus, J., and Smith, J. W. (2000) Ligand binding to integrins. J. Biol. Chem. 275, 21785-21788
36. Hynes, R. O. (2004) The emergence of integrins: a personal and historical perspective. Matrix Biol. 23, 333-340
37. Byzova, T. V., Goldman, C. K., Pampori, N., Thomas, K. A., Bett, A., Shattil, S. J., and Plow, E. F. (2000) A mechanism for modulation of cellular responses to VEGF: activation of the integrins. Mol. Cell 6, 851-860
38. Fernández-Hernando, C., József, L., Jenkins, D., Di Lorenzo, A., and Sessa, W. C. (2009) Absence of Akt1 reduces vascular smooth muscle cell migration and survival and induces features of plaque vulnerability and cardiac dysfunction during atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29, 2033-2040
39. Bialkowska, K., Zaffran, Y., Meyer, S. C., and Fox, J. E. (2003) 14-3-3 ζmediates integrin-induced activation of Cdc42 and Rac: platelet glycoprotein Ib-IX regulates integrin-induced signaling by sequestering 14-3-3 ζ. J. Biol. Chem. 278, 33342-33350
40. Mammoto, A., Mammoto, T., and Ingber, D. E. (2008) Rho signaling and mechanical control of vascular development. Curr. Opin. Hematol. 15, 228-234
41. ten Klooster, J. P., Jaffer, Z. M., Chernoff, J., and Hordijk, P. L. (2006) Targeting and activation of Rac1 are mediated by the exchange factor beta-Pix. J. Cell Biol. 172, 759-769
42. Chittenden, T. W., Claes, F., Lanahan, A. A., Autiero, M., Palac, R. T., Tkachenko, E. V., Elfenbein, A., Ruiz de Almodovar, C., Dedkov, E., Tomanek, R., Li, W., Westmore, M., Singh, J. P., Horowitz, A., Mulligan-Kehoe, M. J., Moodie, K. L., Zhuang, Z. W., Carmeliet, P., and Simons, M. (2006) Selective regulation of arterial branching morphogenesis by synectin. Dev. Cell 10, 783-795
43. Lanahan, A. A., Chittenden, T. W., Mulvihill, E., Smith, K., Schwartz, S., and Simons, M. (2006) Synectin-dependent gene expression in endothelial cells. Physiol. Genomics 27, 380-390
44. Rudic, R. D., Shesely, E. G., Maeda, N., Smithies, O., Segal, S. S., and Sessa, W. C. (1998) Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. J. Clin. Invest. 101, 731-736
45. Dimmeler, S., Fleming, I., Fisslthaler, B., Hermann, C., Busse, R., and Zeiher, A. M. (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399, 601-605
46. Schaffer, M. R., Tantry, U., Gross, S. S., Wasserburg, H. L., and Barbul, A. (1996) Nitric oxide regulates wound healing. J. Surg. Res. 63, 237-240
47. Lee, P. C., Salyapongse, A. N., Bragdon, G. A., Shears, L. L., 2nd, Watkins, S. C., Edington, H. D., and Billiar, T. R. (1999) Impaired wound healing and angiogenesis in eNOS-deficient mice. Am. J. Physiol. 277, H1600-H1608
48. Yu, J., deMuinck, E. D., Zhuang, Z., Drinane, M., Kauser, K., Rubanyi, G. M., Qian, H. S., Murata, T., Escalante, B., and Sessa, W. C. (2005) Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve. Proc. Natl. Acad. Sci. U.S.A. 102, 10999-11004
49. Schleicher, M., Yu, J., Murata, T., Derakhshan, B., Atochin, D., Qian, L., Kashiwagi, S., Di Lorenzo, A., Harrison, K. D., Huang, P. L., and Sessa, W. C. (2009) The Akt1-eNOS axis illustrates the specificity of kinasesubstrate relationships in vivo. Sci. Signal. 2, ra41
50. Fernández-Hernando, C., Ackah, E., Yu, J., Suárez, Y., Murata, T., Iwakiri, Y., Prendergast, J., Miao, R. Q., Birnbaum, M. J., and Sessa, W. C. (2007) Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Cell Metab. 6, 446-457
51. Somanath, P. R., Razorenova, O. V., Chen, J., and Byzova, T. V. (2006) Akt1 in endothelial cell and angiogenesis. Cell Cycle. 5, 512-518
52. Werner-Felmayer, G., Werner, E. R., Fuchs, D., Hausen, A., Reibnegger, G., and Wachter, H. (1990) Tetrahydrobiopterin-dependent formation of nitrite and nitrate in murine fibroblasts. J. Exp. Med. 172, 1599-1607
53. Tzeng, E., Billiar, T. R., Robbins, P. D., Loftus, M., and Stuehr, D. J. (1995) Expression of human inducible nitric oxide synthase in a tetrahydrobiopterin (H4B)-deficient cell line: H4B promotes assembly of enzyme subunits into an active dimer. Proc. Natl. Acad. Sci. U.S.A. 92, 11771-11775
54. Cho, H., Thorvaldsen, J. L., Chu, Q., Feng, F., and Birnbaum, M. J. (2001) Akt1/PKBα is required for normal growth but dispensable for maintenance of glucose homeostasis in mice. J. Biol. Chem. 276, 38349-38352
55. Oganesian, A., Armstrong, L. C., Migliorini, M. M., Strickland, D. K., and Bornstein, P. (2008) Thrombospondins use the VLDL receptor and a nonapoptotic pathway to inhibit cell division in microvascular endothelial cells. Mol. Biol. Cell 19, 563-571
56. Agah, A., Kyriakides, T. R., Lawler, J., and Bornstein, P. (2002) The lack of thrombospondin-1 (TSP1) dictates the course of wound healing in double-TSP1/TSP2-null mice. Am. J. Pathol. 161, 831-839
57. Bouaouina, M., Harburger, D. S., and Calderwood, D. A. (2012) Talin and signaling through integrins. Methods Mol. Biol. 757, 325-347
58. Agah, A., Kyriakides, T. R., and Bornstein, P. (2005) Proteolysis of cellsurface tissue transglutaminase by matrix metalloproteinase-2 contributes to the adhesive defect and matrix abnormalities in thrombospondin-2-null fibroblasts and mice. Am. J. Pathol. 167, 81-88
59. Linnerth-Petrik, N. M., Santry, L. A., Petrik, J. J., and Wootton, S. K. (2014) Opposing functions of akt isoforms in lung tumor initiation and progression. PLoS One 9, e94595
60. Gonzalez, E., and McGraw, T. E. (2009) The Akt kinases: isoform specificity in metabolism and cancer. Cell Cycle 8, 2502-2508
61. Diez, H., Garrido, J. J., and Wandosell, F., (2012) Specific roles of Akt iso forms in apoptosis and axon growth regulation in neurons. PLoS One 7, e32715
62. Somanath, P. R., Chen, J., and Byzova, T. V. (2008) Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing. Angiogenesis 11, 277-288
63. Shiojima, I., and Walsh, K. (2002) Role of Akt signaling in vascular homeostasis and angiogenesis. Circ. Res. 90, 1243-1250
64. Gurtner, G. C., Werner, S., Barrandon, Y., and Longaker, M. T. (2008) Wound repair and regeneration. Nature 453, 314-321
65. Liu, S., Xu, S. W., Blumbach, K., Eastwood, M., Denton, C. P., Eckes, B., Krieg, T., Abraham, D. J., and Leask, A. (2010) Expression of integrin β1 by fibroblasts is required for tissue repair in vivo. J. Cell Sci. 123, 3674-3682
66. Singer, A. J., and Clark, R. A. (1999) Cutaneous wound healing. N. Engl. J. Med. 341, 738-746
67. Lauffenburger, D. A., and Horwitz, A. F. (1996) Cell migration: a physically integrated molecular process. Cell 84, 359-369
68. Ridley, A. J. (2004) Pulling back to move forward. Cell 116, 357-358
69. Zaidel-Bar, R., Itzkovitz, S., Ma'ayan, A., Iyengar, R., and Geiger, B. (2007) Functional atlas of the integrin adhesome. Nat. Cell Biol. 9, 858-867
70. Zaidel-Bar, R., Milo, R., Kam, Z., and Geiger, B. (2007) A paxillin tyrosine phosphorylation switch regulates the assembly and form of cell-matrix adhesions. J. Cell Sci. 120, 137-148
71. Liu, S., Xu, S. W., Kennedy, L., Pala, D., Chen, Y., Eastwood, M., Carter, D. E., Black, C. M., Abraham, D. J., and Leask, A. (2007) FAK is required for TGFβ-induced JNK phosphorylation in fibroblasts: implications for acquisition of a matrix-remodeling phenotype. Mol. Biol. Cell 18, 2169-2178