Transforming growth factor-β and endoglin signaling orchestrate wound healing

Frontiers in Physiology

Volumn 2 NOV, Issue , 2011, Pages

  Valluru, Manoj ^a   Staton, Carolyn A ^a   Reed, Malcolm W R ^a   Brown, Nicola J ^a  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

Author keywords

Angiogenesis; Endoglin; Progenitor cells; Stem cells; TGF ; Wound healing

Indexed keywords

EID: 84863537139     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2011.00089     Document Type: Article

References (134)

1. Aarabi, S., Bhatt, K. A., Shi, Y., Paterno, J., Chang, E. I., Loh, S. A., Holmes, J. W., Longaker, M. T., Yee, H., and Gurtner, G. C. (2007). Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis. FASEB J. 21, 3250-3261.
2. Aiba-Kojima, E., Tsuno, N. H., Inoue, K., Matsumoto, D., Shigeura, T., Sato, T., Suga, H., Kato, H., Nagase, T., Gonda, K., Koshima, I., Takahashi, K., and Yoshimura, K. (2007). Characterization of wound drainage fluids as a source of soluble factors associated with wound healing: comparison with platelet-rich plasma and potential use in cell culture. Wound Repair Regen. 15, 511-520.
3. Ambler, C. A., and Määttä, A. (2009). Epidermal stem cells: location, potential and contribution to cancer. J.Pathol. 217,206-216.
4. Amjad, S. B., Carachi, R., and Edward, M. (2007). Keratinocyte regulation of TGF-beta and connective tissue growth factor expression: a role in suppression of scar tissue formation. Wound Repair Regen. 15,748-755.
5. Asahara, T., Masuda, H., Takahashi, T., Kalka, C., Pastore, C., Silver, M., Kearne, M., Magner, M., and Isner, J. M. (1999). Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculoge-nesis in physiological and pathological neovascularization. Circ. Res. 85, 221-228.
6. Asmis, R., Qiao, M., Rossi, R. R., Cholewa, J., Xu, L., and Asmis, L. M. (2006). Adriamycin promotes macrophage dysfunction in mice. FreeRadic. Biol. Med. 41, 165-174.
7. Bandyopadhyay, B., Fan, J., Guan, S., Li, Y., Chen, M., Woodley, D. T., and Li, W. (2006). A traffic control role for TGFβ3: orchestrating dermal and epidermal cell motility during wound healing. J. Cell Biol. 172,1093-1105.
8. Barbara, N. P., Wrana, J. L., and Letarte, M. (1999). Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-β superfamily. J. Biol. Chem. 274, 584-594.
9. Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H., and Tomic-Canic, M. (2008). Growth factors and cytokines in wound healing. Wound Repair Regen. 16,585-601.
10. Bernabeu, C., Conley, B. A., and Vary, C. P. H. (2007). Novel biochemical pathways of endoglin in vascular cell physiology. J. Cell. Biochem. 102, 1375-1388.
11. Bertolino, P., Deckers, M., Lebrin, F., and ten Dijke, P. (2005). Transforming growth factor-beta signal trans-duction in angiogenesis and vascular disorders. Chest 128, 585S-590S.
12. Bicknell, R., and Harris, A. L. (2004). Novel angiogenic signaling pathways and vascular targets. Annu. Rev. Pharmacol. Toxicol. 44,219-238.
13. Bingle, L, Lewis, C. E., Corke, K. P., and Reed, M. W. R. Brown NJ. (2006). Macrophages promote angiogenesis in human breast tumour spheroids in vivo. Br. J. Cancer 94,101-107.
14. Blanpain, C., and Fuchs, E. (2009). Epidermal homeostasis: a balancing act of stem cells in the skin. Nat. Rev. Mol. Cell Biol. 10,207-217.
15. Bot, P. T. G., Hoefer, I. E., Sluijter, J. P. G., van Vliet, P., Smits, A. M., Lebrin, E, Moll, F., de Vries, J.-P., Doeven dans, P., Piek, J. J., Pasterkamp, G., and Goumans, M. J. (2009). Increased expression of the transforming growth factor-{beta} signaling pathway, endoglin, and early growth response-1 in stable plaques. Stroke 40,439-447.
16. Botchkarev,V.A. (2003).Bonemorpho-genetic proteins and their antagonists in skin and hair follicle biology. J. Invest. Dermatol. 120, 36-47.
17. Brown, N. J., Smyth, E. A. E., Cross, S. S., and Reed, M. W. R. (2002). Angiogenesis induction and regression in human surgical wounds. Wound Repair Regen. 10,245-251.
18. Canic, M. T., Ågren, M. S., and Alvarez, O. M. (2004). Epidermal repair and the chronic wound, in The Epidermis in Wound Healing, eds D. T. Rovee and H. I. Maibach (Boca Raton, FL: CRC Press LLC), 25-58.
19. Chapkin, R. S., Wang, N., Fan, Y. Y., Lupton, J. R., and Prior, I. A. (2008). Docosahexaenoic acid alters the size and distribution of cell surface microdomains. Biochim. Biophys.Acta 1778,466-471.
20. Chen, C.-Z., Li, L., Li, M., and Lodish, H. F. (2003). The endoglin positive sca- 1positive rhodaminelow phenotype defines a near-homogeneous population of long-term repopulating hematopoietic stem cells. Immunity 19,525-533.
21. Clayton, E., Doupe, D. P., Klein, A. M., Winton, D. J., Simons, B. D., and Jones, P. H. (2007). A single type of progenitor cell maintains normal epidermis. Nature 446, 185-189.
22. Conconi, M. T., Burra, P., Di Liddo, R., Calore, C., Turetta, M., Bellini, S., Bo, P., Nussdorfer, G. G., and Parnigotto, P. P. (2006). CD105(+) cells from Wharton's jelly show in vitro and in vivo myogenic differentiative potential. Int. J. Mol. Med. 18, 1089-1096.
23. Conley, B. A., Koleva, R., Smith, J. D., Kacer, D., Zhang, D., Bernabéu, C., and Vary, C. P. H. (2004). Endoglin controls cell migration and composition of focal adhesions: function of the cytosolic domain. J. Biol. Chem. 279, 27440-27449.
24. Conley, B. A., Smith, J. D., Guerrero-Esteo, M., Bernabeu, C., and Vary, C. P. (2000). Endoglin, a TGF-beta receptor-associated protein, is expressed by smooth muscle cells in human atherosclerotic plaques. Atherosclerosis 153, 323-335.
25. Crisan, M., Yap, S., Casteilla, L., Chen, C., Corselli, M., Park, T., Andriolo, G., Sun, B., Zheng, B., and Zhang, L. (2008). A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3, 301-313.
26. Crowe, M. J., Doetschman, T., and Greenhalgh, D. G. (2000). Delayed wound healing in immunodeficient TGF-[beta]1 knockout mice. 115, 3-11.
27. Dabiri, G., and DiPersio, C. M. (2005). Matrix metalloproteinases (MMPs), in Wound Healing, eds A. F. Falabella and R. S. Kirsner (Boca Raton: Taylor and Francis Group), 49-56.
28. Dallas, N. A., Samuel, S., Xia, L., Fan, F., Gray, M. J., Lim, S. J., and Ellis, L. M. (2008).Endoglin (CD105):amarker of tumor vasculature and potential target for therapy. Clin. Cancer Res. 14, 1931-1937.
29. Faler, B. J., Macsata, R. A., Plummer, D., Mishra, L., and Sidawy, A. N. (2006). Transforming growth factor-{beta} and wound healing. Per-spect. Vasc. Surg. Endovasc. Ther. 18, 55-62.
30. Garrett, Q., Khaw, P. T., Blalock, T. D., Schultz, G. S., Grotendorst, G. R., and Daniels, J. T. (2004). Involvement of CTGF in TGF-{beta}1-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress. Invest. Ophthalmol. Vis. Sci. 45, 1109-1116.
31. Gehling, U. M. (2006). Hemangioblasts and their progeny. Methods Enzymol. 419, 179-193.
32. Gerritsen, M. E. (2008). Angiogenesis, in Handbook of Physiology: Micro-circulation, eds R. F. Tuma, W. N. Duran, and K. Ley (Cambridge, MA: Elsevier Science), 351-372.
33. Ghassemifar, M., Tarnuzzer, R., Chegini, N., Tarpila, E., Schultz, G., and Franzén, L. (1997). Expression of alpha-smooth muscle actin, TGF-β1 and TGF-β type II receptor during connective tissue contraction. In vitro Cell. Dev. Biol.- Anim. 33, 622-627.
34. Gillard, J. A., Reed, M. W. R., Buttle, D., Cross, S. S., and Brown, N. J. (2004). Matrix metalloproteinase activity and immunohistochemical profile of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human dermal wound healing. Wound Repair Regen. 12,295-304.
35. Gomes, I., Dale, C. S., Casten, K., Geigner, M. A., Gozzo, F. C., Ferro, E. S., Heimann, A. S., and Devi, L. A. (2010). Hemoglobin-derived peptides as novel type of bioactive signaling molecules. AAPS J. 12, 658-669.
36. Gougos, A., and Letarte, M. (1990). Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J. Biol. Chem. 265, 8361-8364.
37. Groppe, J., Hinck, C. S., Samavarchi-Tehrani, P., Zubieta, C., Schuer-mann, J. P., Taylor, A. B., Schwarz, P. M., Wrana, J. L., and Hinck, A. P. (2008). Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding. Mol. Cell 29, 157-168.
38. Guo, B., Kumar, S., Li, C., Slevin, M., and Kumar, P. (2004a). CD 105 (endoglin), apoptosis, and stroke. Stroke 35, e94-e95.
39. Guo, B., Slevin, M., Li, C., Paramesh-war, S., Liu, D., Kumar, P., Bernabeu, C., and Kumar, S. (2004b). CD 105 inhibits transforming growth factor-beta-Smad3 signalling. Anticancer Res. 24, 1337-1345.
40. Gurtner, G. C., Werner, S., Barran-don, Y., and Longaker, M. T. (2008). Wound repair and regeneration. Nature 453, 314-321.
41. Harvey, K. A., Paranavitana, C. N., Zaloga, G. P., and Siddiqui, R. A. (2007). Diverse signaling pathways regulate fibroblast differentiation and transformation through Rho kinase activation. J. Cell. Physiol. 211,353-363.
42. He, W., Dorn, D. C., Erdjument-Bromage, H., Tempst, P., Moore, M. A., and Massague, J. (2006). Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway. Cell 125, 929-941.
43. Hill, J. M., Zalos, G., Halcox, J. P. J., Schenke, W H., Waclawiw, M. A., Quyyumi, A. A., and Finkel, T. (2003). Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med. 348, 593-600.
44. Hinz, B. (2007). Formation and function of the myofibroblast during tissue repair. J. Invet. Dermatol. 127, 526-537.
45. Holderfield, M. T., and Hughes, C. C. W (2008). Crosstalk between vascular endothelial growth factor, notch, and transforming growth factor-{beta} in vascular morphogenesis. Circ. Res. 102, 637-652.
46. Hosokawa, R., Urata, M. M., Ito, Y., Bringas, P., and Chai, Y (2005). Functional significance of Smad2 in regulating basal keratinocyte migration during wound healing. J. Invest. Dermatol. 125, 1302-1309.
47. Hung, S. C., Kuo, P. Y., Chang, C. F., Chen, T. H., and Ho, L. L. (2006). Alpha-smooth muscle actin expression and structure integrity in chon-drogenesis of human mesenchymal stem cells. Cell Tissue Res. 324, 457-466.
48. Itoh, S., and ten Dijke, P. (2007). Negative regulation of TGF-beta receptor/Smad signal transduction. Curr. Opin. Cell Biol. 19,176-184.
49. Jian, H., Shen, X., Liu, I., Semenov, M., He, X., and Wang, X. F. (2006). Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells. Genes Dev. 20, 666-674.
50. Jin, H. J., Park, S. K., Oh, W., Yang, Y. S., Kim, S. W., and Choi, S. J. (2009). Down-regulation of CD 105 is associated with multilineage differentiation in human umbilical cord blood-derived mesenchymal stem cells. Biochem. Biophys. Res. Commun. 381,676-681.
51. Kang, J. S., Liu, C., and Derynck, R. (2009). New regulatory mechanisms of TGF-beta receptor function. Trends Cell Biol. 19, 385-394.
52. Khakoo, A. Y., and Finkel, T. (2005). Endothelial progenitor cells. Annu. Rev. Med. 56,79-101.
53. Kilarski, W W, Samolov, B., Petersson, L., Kvanta, A., and Gerwins, P. (2009). Biomechanical regulation of blood vessel growth during tissue vascularization. Nat. Med. 15, 657-664.
54. Kimmel, A. R., Brasaemle, D. L., McAndrews-Hill, M., Sztalryd, C., and Londos, C. (2010). Adoption of PERILIPIN as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins. J. Lipid Res. 51, 468-471.
55. Kitisin, K., Saha, T., Blake, T., Golestaneh, N., Deng, M., Kim, C., Tang, Y., Shetty, K., Mishra, B., and Mishra, L. (2007). TGF-beta signaling in development. Sci. STKE 2007, cm1.
56. Klass, B. R., Grobbelaar, A. O., and Rolfe, K. J. (2009). Transforming growth factor β1 signalling, wound healing and repair: a multifunctional cytokine with clinical implications for wound repair, a delicate balance. Postgrad. Med. J. 85, 9-14.
57. Koleva, R. I., Conley, B. A., Romero, D., Riley, K. S., Marto, J. A., Lux, A., and Vary, C. P. H. (2006). Endoglin structure and function.J. Biol. Chem. 281, 25110-25123.
58. Kulkarni, A. B., Huh, C. G., Becker, D., Geiser, A., Lyght, M., Flanders, K. C., Roberts, A. B., Sporn, M. B., Ward, J. M., and Karlsson, S. (1993). Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl. Acad. Sci. U.S.A. 90, 770-774.
59. Kumar, I., Staton, C. A., Cross, S. S., Reed, M. W. R., and Brown, N. J. (2009). Angiogenesis, vascular endothelial growth factor and its receptors in human surgical wounds. Br. J. Surg. 96, 1484-1491.
60. Lancrin, C., Sroczynska, P., Stephen-son, C., Allen, T., Kouskoff, V., and Lacaud, G. (2009). The hae-mangioblast generates haematopoietic cells through a haemogenic endothelium stage. Nature 457, 892-895.
61. Le, B. V., Franke, D., Svergun, D. I., Han, T., Hwang, H.-Y., and Kim, K. K. (2009). Structural and functional characterization of soluble endoglin receptor. Biochem. Biophys. Res. Commun. 383,386-391.
62. Lebrin, F., Goumans, M.-J., Jonker, L., Carvalho, R. L. C., Valdimarsdot-tir, G., Thorikay, M., Mummery, C., Arthur, H. M., and Dijke, P. t. (2004). Endoglin promotes endothelial cell proliferation and TGF-[beta]/ALK1 signal transduction. EMBO J. 23, 4018-4028.
63. Lechapt-Zalcman, E., Pruliere-Escabasse, V., Advenier, D., Galiacy, S., Charriere-Bertrand, C., Coste, A., Harf, A., d'Ortho, M. P., and Escud-ier, E. (2006). Transforming growth factor-beta1 increases airway wound repair via MMP-2 upregulation: a new pathway for epithelial wound repair? Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L1277-L1282.
64. Lechler, T., and Fuchs, E. (2005). Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 437, 275-280.
65. Lee, N. Y., and Blobe, G. C. (2007). The Interaction of endoglin with β-arrestin2 regulates transforming growth factor-β-mediated erk activation and migration in endothelial cells. J. Biol. Chem. 282, 21507-21517.
66. Lee, N. Y., Ray, B., How, T., and Blobe, G. C. (2008). Endoglin promotes transforming growth factor beta-mediated Smad 1/5/8 signaling and inhibits endothelial cell migration through its association with GIPC. J. Biol. Chem. 283, 32527-32533.
67. Lee, P., Lee, D. J., Chan, C., Chen, S. W., Ch'en, I., and Jamora, C. (2009). Dynamic expression of epidermal caspase 8 simulates a wound healing response. Nature 458, 519-523.
68. Li, C., Issa, R., Kumar, P., Hampson, I. N., Lopez-Novoa, J. M., Bernabeu, C., and Kumar, S. (2003). CD105 prevents apoptosis in hypoxic endothelial cells.J. Cell Sci. 116,2677-2685.
69. Li, F., Huang, Q., Chen, J., Peng, Y., Roop, D. R., Bedford, J. S., and Li, C. Y (2010). Apoptotic cells activate the phoenix rising pathway to promote wound healing and tissue regeneration. Sci. Signal. 3, ra13.
70. Liu, M., and Horowitz, A. (2006). A PDZ-binding motif as a critical determinant of Rho guanine exchange factor function and cell phenotype. Mol. Biol. Cell 17, 1880-1887.
71. Liu, T., and Feng, X. H. (2010). Regulation of TGF-beta signalling by protein phosphatases. Biochem. J. 430, 191-198.
72. Llorca, O., Trujillo, A., Blanco, E J., and Bernabeu, C. (2007). Structural model of human endoglin, a trans-membrane receptor responsible for hereditary hemorrhagic telangiecta-sia. J. Mol. Biol. 365, 694-705.
73. Lonn, P., Moren, A., Raja, E., Dahl, M., and Moustakas, A. (2009). Regulating the stability of TGFbeta receptors andSmads. CellRes. 19,21-35.
74. Lutz, M., and Knaus, P. (2002). Integration of the TGF-beta pathway into the cellular signalling network. Cell. Signal. 14, 977-988.
75. Ma, J., Wang, Q., Fei, T., Han, J.-D. J., and Chen, Y.-G. (2007). MCP-1 mediates TGF-{beta}-induced angiogenesis by stimulating vascular smooth muscle cell migration. Blood 109, 987-994.
76. Machado, M. J., and Mitchell, C. A. (2011). Temporal changes in microvessel leakiness during wound healing discriminated by in vivo fluorescence recovery after photo-bleaching. J. Physiol. (Lond.) 589, 4681-4696.
77. Mahmoud, M., Borthwick, G. M., His-lop, A. A., and Arthur, H. M. (2009). Endoglin and activin receptor-like-kinase 1 are co-expressed in the distal vessels of the lung: implications for two familial vascular dys-plasias, HHT and PAH. Lab. Invest. 89, 15-25.
78. Mani, S., Guo, W., Liao, M., Eaton, E., Ayyanan, A., Zhou, A., Brooks, M., Reinhard, F., Zhang, C., and Shipitsin, M. (2008). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133,704-715.
79. Mansilla, E., MarIn, G. H., Drago, H., Sturla, F., Salas, E., Gardiner, C., Bossi, S., Lamonega, R., Guzmán, A., Nuñez, A., Gil, M. A., Pic-cinelli, G., Ibar, R., and Soratti, C. (2006). Bloodstream cells phenotyp-ically identical to human mesenchy-mal bone marrow stem cells circulate in large amounts under the influence of acute large skin damage: new evidence for their use in regenerative medicine. Transplant. Proc. 38, 967-969.
80. Meurer, S. K., Tihaa, L., Borkham-Kamphorst, E., and Weiskirchen, R. (2011). Expression and functional analysis of endoglin in isolated liver cells and its involvement in fibro-genic smad signalling. Cell. Signal. 23, 683-699.
81. Morasso, M. I., and Tomic-Canic, M. (2005). Epidermal stem cells: the cradle of epidermal determination, differentiation and wound healing. Biol. Cell 97,173-183.
82. Moustakas,A.,andHeldin,C.H. (2009). The regulation of TGFbeta signal transduction. Development 136, 3699-3714.
83. Nath, R. K., LaRegina, M., Markham, H., Ksander, G. A., and Weeks, P. M. (1994). The expression of transforming growth factor type beta in fetal and adult rabbit skin wounds. J. Pediatr. Surg. 29, 416-421.
84. Nikiteas, N. I., Tzanakis, N., Theodor-opoulos, G., Atsaves, V., Christoni, Z., Karakitsos, P., Lazaris, A. C., Papachristodoulou, A., Klonaris, C., and Gazouli, M. (2007). Vascular endothelial growth factor and endoglin (CD-105) in gastric cancer. Gastric Cancer 10,12-17.
85. Okuda, K., Murata, M., Sugimoto, M., Saito, Y., Kabasawa, Y., Yoshie, H., Saku, T., and Hara, K. (1998). TGF-beta1 influences early gingival wound healing in rats: an immuno-histochemical evaluation of stromal remodelling by extracellular matrix molecules and PCNA. J. Oral Pathol. Med. 27, 463-469.
86. Owens, P., Han, G., Li, A. G., and Wang, X. J. (2008). The role of Smads in skin development. J. Invest. Derma-tol. 128, 783-790.
87. Oxmann, D., Held-Feindt, J., Stark, A. M., Hattermann, K., Yoneda, T., and Mentlein, R. (2008). Endoglin expression in metastatic breast cancer cells enhances their invasive phenotype. Oncogene 27, 3567-3575.
88. Padgett, R. W., and Reiss, M. (2007). TGFbeta superfamily signaling: notes from the desert. Development 134, 3565-3569.
89. Pera, M. F., and Tam, P. P. (2010). Extrinsic regulation of pluripotent stem cells. Nature 465, 713-720.
90. Perlingeiro, R. C. R. (2007). Endoglin is required for hemangioblast and early hematopoietic development. Development 134, 3041-3048.
91. Pronk, C., Rossi, D., Mansson, R., Attema, J., Norddahl, G., Chan, C., Sigvardsson, M., Weissman, I., and Bryder, D. (2007). Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy. Cell Stem Cell 1,428-442.
92. Quesada, I. M., Del Bas, J. M., Blade, C., Ardevol, A., Blay, M., Salvado, M. J., Pujadas, G., Fernandez-Larrea, J., and Arola, L. (2007). Grape seed procyanidins inhibit the expression of metallothione in genes in human HepG2 cells. Genes Nutr. 2, 105-109.
93. Riekstina, U., Muceniece, R., Cakstina, I., Muiznieks, I., and Ancans, J. (2008). Characterization of human skin-derived mesenchymal stem cell proliferation rate in different growth conditions. Cytotechnology 58,153-162.
94. Ross, S., and Hill, C. S. (2008). How the Smads regulate transcription. Int. J. Biochem. Cell Biol. 40, 383-408.
95. Ruscetti, F. W., Akel, S., and Bartelmez, S. H. (2005). Autocrine transforming growth factor-beta regulation of hematopoiesis: many outcomes that depend on the context. Oncogene 24, 5751-5763.
96. Sánchez-Elsner, T., Botella, L. M., Velasco, B., Langa, C., and Bernabéu, C. (2002). Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways. J. Biol. Chem. 277, 43799-43808.
97. Sandlund, J., Hedberg, Y., Bergh, A., Grankvist, K., Ljungberg, B., and Rasmuson, T. (2006). Endoglin (CD 105) expression in human renal cell carcinoma. BJU Int. 97, 706-710.
98. Santibanez, J. F., Letamendia, A., Perez-Barriocanal, F., Silvestri, C., Saura, M., Vary, C. P. H., Lopez-Novoa, J. M., Attisano, L., and Bernabeu, C. (2007). Endoglin increases eNOS expression by modulating Smad2 protein levels and Smad2-dependent TGF-beta signaling. J. Cell. Physiol. 210,456-468.
99. Schmid, P., Cox, D., Bilbe, G., McMas-ter, G., Morrison, C., Stähelin, H., Lüscher, N., and Seiler, W. (1993). TGF-beta s and TGF-beta type II receptor in human epidermis: differential expression in acute and chronic skin wounds. J. Pathol. 171, 191-197.
100. Schultz, G. S. (2007). The physiology of wound bed preparation, in Surgical Wound Healing and Management, eds M. S. Granick and R. L. Gamelli (London: Informa Healthcare, Inc.), 1-16.
101. Semenza, G. L. (2007). Regulation of angiogenesis and arteriogenesis by hypoxia-inducible factor-1,in Modern Concepts in Angiogenesis, eds M. Simons and G. M. Rubanyi (London: Imperial College Press), 175-216.
102. Shephard, P., Martin, G., Smola-Hess, S., Brunner, G., Krieg, T., and Smola, H. (2004). Myofibroblast differentiation is induced in keratinocyte-fibroblast co-cultures and is antagonistically regulated by endogenous transforming growth factor-{beta} and interleukin-1. Am. J. Pathol. 164, 2055-2066.
103. Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., Allen, R., Sidman, C., Proetzel, G., Calvin, D., Annun-ziata, N., and Doetschman, T. (1992). Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359, 693-699.
104. Smith, P. C, Caceres, M., and Martinez, J. (2006). Induction of the myofi-broblastic phenotype in human gin-gival fibroblasts by transforming growth factor-β1: role of RhoA-ROCK and c-Jun N-terminal kinase signaling pathways. J. Peri-odont. Res. 41,418-425.
105. Tang, H., Low, B., Rutherford, S. A., and Hao, Q. (2005). Thrombin induces endocytosis of endoglin and type-II TGF-beta receptor and down-regulation of TGF-beta signaling in endothelial cells. Blood 105, 1977-1985.
106. Tao, S., and Sampath, K. (2010). Alternative splicing of SMADs in differentiation and tissue homeostasis. Dev. Growth Differ. 52, 335-342.
107. Ten Dijke, P., Goumans, M.-J., and Pardali, E. (2008). Endoglin in angiogenesis and vascular diseases. Angiogenesis 11, 79-89.
108. Thiery, J. P., and Sleeman, J. P. (2006). Complex networks orchestrate epithelial-mesenchymal transitions. Nat. Rev. Mol. Cell Biol. 7, 131-142.
109. Thompson, H. G. R., Mih, J. D., Krasieva, T. B., Tromberg, B. J., and George, S. C. (2006). Epithelial-derived TGF-beta2 modulates basal and wound-healing subepithelial matrix homeostasis. Am. J. Physiol. Lung Cell. Mol. Physiol. 291, L1277-L1285.
110. Tian, Y., Tang, S., and Luo, S. (2000). A study on the expressions and the correlation of TGF-beta and alpha-SMA in scars. Zhonghua Zheng Xing WaiKeZaZhi 16,75-77.
111. Torsney, E., Charlton, R., Parums, D., Collis, M., and Arthur, H. M. (2002). Inducible expression of human endoglin during inflammation and wound healing in vivo. Inflamm. Res. 51, 464-470.
112. Tredget, E. B., Demare, J., Chandran, G., Tredget, E. E., Yang, L., and Ghahary, A. (2005). Transforming growth factor-beta and its effect on reepithe-lialization of partial-thickness ear wounds in transgenic mice. Wound Repair Regen. 13,61-67.
113. Turner, C. H., Chandran, A., and Pida-parti, R. M. (1995). The anisotropy of osteonal bone and its ultrastructural implications. Bone 17, 85-89.
114. Tyrone, J. W., Marcus, J. R., Bonomo, S. R., Mogford, J. E., Xia, Y., and Mustoe, T. A. (2000). Transforming growth factor {beta}3 promotes fas-cial wound healing in a new animal model. Arch. Surg. 135,1154-1159.
115. Urbich, C., and Dimmeler, S. (2004). Endothelial progenitor cells: characterization and role in vascular biology. Circ. Res. 95, 343-353.
116. Valluru, M., Brown, N. J., Cross, S. S., Reed, M. W., and Staton, C. A. (2011). Blood vessel characterisation in human dermal wound repair and scarring. Br. J. Dermatol. 165, 221-224.
117. van Laake, L. W., van den Driesche, S., Post, S., Feijen, A., Jansen, M. A., Driessens, M. H., Mager, J. J., Snijder, R. J., Westermann, C. J. J., Doeven-dans, P. A., van Echteld, C. J., ten Dijke, P., Arthur, H. M., Goumans, M. J., Lebrin, F., and Mummery, C. L. (2006). Endoglin has a crucial role in blood cell-mediated vascular repair. Circulation 114,2288-2297.
118. van Poll, D., Parekkadan, B., Borel Rinkes, I., Tilles, A., and Yarmush, M. (2008). Mesenchymal stem cell therapy for protection and repair of injured vital organs. Cell. Mol. Bioeng. 1,42-50.
119. Vaughan, M. B., Howard, E. W., and Tomasek, J. J. (2000). Transforming growth factor-[beta]1 promotes the morphological and functional differentiation of the myofibroblast. Exp. Cell Res. 257, 180-189.
120. Venkatesha, S., Toporsian, M., Lam, C., Hanai, J., Mammoto, T., Kim, Y. M., Bdolah, Y., Lim, K. H., Yuan, H. T., Libermann, T. A., Stillman, I. E., Roberts, D., D'Amore, P. A., Epstein, F. H., Sellke, F. W., Romero, R., Sukhatme, V. P., Letarte, M., and Karumanchi, S. A. (2006). Soluble endoglin contributes to the patho-genesis of preeclampsia. Nat. Med. 12, 642-649.
121. Wahl, S. M., Hunt, D. A., Wakefield, L. M., McCartney-Francis, N., Wahl, L. M., Roberts, A. B., and Sporn, M. B. (1987). Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc. Natl. Acad. Sci. U.S.A. 84,5788-5792.
122. Wang, J., Jiao, H., Stewart, T. L., Shankowsky, H. A., Scott, P. G., and Tredget, E. E. (2007a). Increased TGF-β–producing CD4+ T lymphocytes in postburn patients and their potential interaction with dermal fibroblasts in hypertrophic scarring. Wound Repair Regen. 15,530-539.
123. Wang, J. F., Jiao, H., Stewart, T. L., Shankowsky, H. A., Scott, P. G., and Tredget, E. E. (2007b). Fibro-cytes from burn patients regulate the activities of fibroblasts. Wound Repair Regen. 15, 113-121.
124. Watabe, T., and Miyazono, K. (2009). Roles of TGF-beta family signaling in stem cell renewal and differentiation. Cell Res. 19, 103-115.
125. Werner, S., Krieg, T., and Smola, H. (2007). Keratinocyte-fibroblast interactions in wound healing. J. Invest. Dermatol. 127, 998-1008.
126. Wrighton, K. H., Lin, X., and Feng, X. H. (2009). Phospho-control of TGF-beta superfamily signaling. Cell Res. 19, 8-20.
127. Wu, J., Basha, M. R., and Zawia, N. H. (2008). The environment, epige-netics and amyloidogenesis. J. Mol. Neurosci. 34, 1-7.
128. Xie, L., Law, B. K., Chytil, A. M., Brown, K. A., Aakre, M. E., and Moses, H. L. (2004). Activation of the Erk pathway is required for TGF-β1-induced EMT in vitro. Neoplasia 6, 603-610.
129. Xiong, J.-W (2008). Molecular and developmental biology of the hemangioblast. Dev. Dyn. 237, 1218-1231.
130. Yuji, Y., Vincent, H., Satoshi, I., Kuni- hiko, Y., and Ichiro, K. (2005). Mesenchymal-epithelial interactions in the skin: aiming for site-specific tissue regeneration. J. Dermatol. Sci. 40,1-9.
131. Zhang, Y E. (2009). Non-Smad pathways in TGF-beta signaling. Cell Res. 19, 128-139.
132. Zhu, X.-Y., Fang, C.-H., Zhang, L.-Y., Zuo, D.-M., and Chen, Z.-L. (2005). Expressions and role of endoge-netic matrix metalloproteinases-9 and transforming growth factor-beta during wound healing of blast injury. Di Yi Jun Yi Da Xue Xue 25, 844-846.
133. Zhu, Y., Sun, Y., Xie, L., Jin, K., Sheibani, N., and Greenberg, D. A. (2003). Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvas-cular endothelial cells. Stroke 34, 2483-2488.
134. Zvaifler, N. J., Marinova-Mutafchieva, L., Adams, G., Edwards, C. J., Moss, J., Burger, J. A., and Maini, R. N. (2000). Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2, 477-488.