Endoglin Haploinsufficiency Promotes Fibroblast Accumulation during Wound Healing through Akt Activation

PLoS ONE

Volumn 8, Issue 1, 2013, Pages

  Pericacho, Miguel ^a   Velasco, Soraya ^a   Prieto, Marta ^a   Llano, Elena ^a   López Novoa, José M ^a,b   Rodríguez Barbero, Alicia ^a,b  

^a UNIVERSITY OF SALAMANCA   (Spain)

^b INSTITUTO DE INVESTIGACIÓN BIOMÉDICA DE SALAMANCA IBSAL   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ENDOGLIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SMAD2 PROTEIN;

ANIMAL CELL; ANIMAL CELL CULTURE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BIOACCUMULATION; CELL FUNCTION; CELL MIGRATION; CELL PROLIFERATION; CELL TRANSFORMATION; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME LOCALIZATION; ENZYME PHOSPHORYLATION; ENZYME REGULATION; FIBROSIS; HAPLOINSUFFICIENCY; HETEROZYGOTE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; SCAR; SIGNAL TRANSDUCTION; SKIN FIBROBLAST; WOUND HEALING;

ANIMALS; CICATRIX; FIBROBLASTS; HAPLOINSUFFICIENCY; HETEROZYGOTE; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MICE; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; SKIN; TRANSCRIPTIONAL ACTIVATION; WOUND HEALING;

MURINAE; MUS;

EID: 84872552236     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0054687     Document Type: Article

References (72)

1. Sorrell JM, Caplan AI, (2004) Fibroblast heterogeneity: more than skin deep. J Cell Sci 117: 667-675.
2. Gurtner GC, Werner S, Barrandon Y, Longaker MT, (2008) Wound repair and regeneration. Nature 453: 314-321.
3. Desmouliere A, Redard M, Darby I, Gabbiani G, (1995) Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol 146: 56-66.
4. Hinz B, (2007) Formation and function of the myofibroblast during tissue repair. J Invest Dermatol 127: 526-537.
5. Valluru M, Staton CA, Reed MW, Brown NJ, (2011) Transforming Growth Factor-beta and Endoglin Signaling Orchestrate Wound Healing. Front Physiol 2: 89.
6. Gougos A, Letarte M, (1990) Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 265: 8361-8364.
7. Lopez-Novoa JM, Bernabeu C, (2010) The physiological role of endoglin in the cardiovascular system. Am J Physiol Heart Circ Physiol 299: H959-974.
8. ten Dijke P, Goumans MJ, Pardali E, (2008) Endoglin in angiogenesis and vascular diseases. Angiogenesis 11: 79-89.
9. Conley BA, Koleva R, Smith JD, Kacer D, Zhang D, et al. (2004) Endoglin controls cell migration and composition of focal adhesions: function of the cytosolic domain. J Biol Chem 279: 27440-27449.
10. Bernabeu C, Conley BA, Vary CP, (2007) Novel biochemical pathways of endoglin in vascular cell physiology. J Cell Biochem 102: 1375-1388.
11. Leask A, Abraham DJ, Finlay DR, Holmes A, Pennington D, et al. (2002) Dysregulation of transforming growth factor beta signaling in scleroderma: overexpression of endoglin in cutaneous scleroderma fibroblasts. Arthritis Rheum 46: 1857-1865.
12. Clemente M, Nunez O, Lorente R, Rincon D, Matilla A, et al. (2006) Increased intrahepatic and circulating levels of endoglin, a TGF-beta1 co-receptor, in patients with chronic hepatitis C virus infection: relationship to histological and serum markers of hepatic fibrosis. J Viral Hepat 13: 625-632.
13. Meurer SK, Tihaa L, Borkham-Kamphorst E, Weiskirchen R, (2011) Expression and functional analysis of endoglin in isolated liver cells and its involvement in fibrogenic Smad signalling. Cell Signal 23: 683-699.
14. Burke JP, Watson RW, Mulsow JJ, Docherty NG, Coffey JC, et al. (2010) Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts. Br J Surg 97: 892-901.
15. Chen K, Mehta JL, Li D, Joseph L, Joseph J, (2004) Transforming growth factor beta receptor endoglin is expressed in cardiac fibroblasts and modulates profibrogenic actions of angiotensin II. Circ Res 95: 1167-1173.
16. Roy-Chaudhury P, Simpson JG, Power DA, (1997) Endoglin, a transforming growth factor-beta-binding protein, is upregulated in chronic progressive renal disease. Exp Nephrol 5: 55-60.
17. Rodriguez-Pena A, Prieto M, Duwel A, Rivas JV, Eleno N, et al. (2001) Up-regulation of endoglin, a TGF-beta-binding protein, in rats with experimental renal fibrosis induced by renal mass reduction. Nephrol Dial Transplant 16Suppl 1: 34-39.
18. Rodriguez-Pena A, Eleno N, Duwell A, Arevalo M, Perez-Barriocanal F, et al. (2002) Endoglin upregulation during experimental renal interstitial fibrosis in mice. Hypertension 40: 713-720.
19. Docherty NG, Lopez-Novoa JM, Arevalo M, Duwel A, Rodriguez-Pena A, et al. (2006) Endoglin regulates renal ischaemia-reperfusion injury. Nephrol Dial Transplant 21: 2106-2119.
20. Diez-Marques L, Ortega-Velazquez R, Langa C, Rodriguez-Barbero A, Lopez-Novoa JM, et al. (2002) Expression of endoglin in human mesangial cells: modulation of extracellular matrix synthesis. Biochim Biophys Acta 1587: 36-44.
21. Lastres P, Letamendia A, Zhang H, Rius C, Almendro N, et al. (1996) Endoglin modulates cellular responses to TGF-beta 1. J Cell Biol 133: 1109-1121.
22. Obreo J, Diez-Marques L, Lamas S, Duwell A, Eleno N, et al. (2004) Endoglin expression regulates basal and TGF-beta1-induced extracellular matrix synthesis in cultured L6E9 myoblasts. Cell Physiol Biochem 14: 301-310.
23. Rodriguez-Barbero A, Obreo J, Eleno N, Rodriguez-Pena A, Duwel A, et al. (2001) Endoglin expression in human and rat mesangial cells and its upregulation by TGF-beta1. Biochem Biophys Res Commun 282: 142-147.
24. Lebrin F, Goumans MJ, Jonker L, Carvalho RL, Valdimarsdottir G, et al. (2004) Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction. Embo J 23: 4018-4028.
25. Scherner O, Meurer SK, Tihaa L, Gressner AM, Weiskirchen R, (2007) Endoglin differentially modulates antagonistic transforming growth factor-beta1 and BMP-7 signaling. J Biol Chem 282: 13934-13943.
26. Velasco S, Alvarez-Munoz P, Pericacho M, Dijke PT, Bernabeu C, et al. (2008) L- and S-endoglin differentially modulate TGFbeta1 signaling mediated by ALK1 and ALK5 in L6E9 myoblasts. J Cell Sci 121: 913-919.
27. Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C, (2002) Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II. J Biol Chem 277: 29197-29209.
28. Morris E, Chrobak I, Bujor A, Hant F, Mummery C, et al. (2011) Endoglin promotes TGF-beta/Smad1 signaling in scleroderma fibroblasts. J Cell Physiol 226: 3340-3348.
29. Scharpfenecker M, Floot B, Russell NS, Ten Dijke P, Stewart FA, (2009) Endoglin haploinsufficiency reduces radiation-induced fibrosis and telangiectasia formation in mouse kidneys. Radiother Oncol 92: 484-491.
30. Arthur HM, Ure J, Smith AJ, Renforth G, Wilson DI, et al. (2000) Endoglin, an ancillary TGFbeta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development. Dev Biol 217: 42-53.
31. Bourdeau A, Dumont DJ, Letarte M, (1999) A murine model of hereditary hemorrhagic telangiectasia. J Clin Invest 104: 1343-1351.
32. Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, et al. (1999) Defective angiogenesis in mice lacking endoglin. Science 284: 1534-1537.
33. Institute of Laboratory Animal Resources (U.S.) (1996) Guide for the care and use of laboratory animals. [7th ed. Washington, D.C.: National Academy Press. xii, 125 p.
34. Jerkic M, Rivas-Elena JV, Prieto M, Carron R, Sanz-Rodriguez F, et al. (2004) Endoglin regulates nitric oxide-dependent vasodilatation. Faseb J 18: 609-611.
35. Persson U, Izumi H, Souchelnytskyi S, Itoh S, Grimsby S, et al. (1998) The L45 loop in type I receptors for TGF-beta family members is a critical determinant in specifying Smad isoform activation. FEBS Lett 434: 83-87.
36. Ge AZ, Butcher EC, (1994) Cloning and expression of a cDNA encoding mouse endoglin, an endothelial cell TGF-beta ligand. Gene 138: 201-206.
37. Robledo MM, Ursa MA, Sanchez-Madrid F, Teixido J, (1998) Associations between TGF-beta1 receptors in human bone marrow stromal cells. Br J Haematol 102: 804-811.
38. Perez-Gomez E, Eleno N, Lopez-Novoa JM, Ramirez JR, Velasco B, et al. (2005) Characterization of murine S-endoglin isoform and its effects on tumor development. Oncogene 24: 4450-4461.
39. Letamendia A, Lastres P, Botella LM, Raab U, Langa C, et al. (1998) Role of endoglin in cellular responses to transforming growth factor-beta. A comparative study with betaglycan. J Biol Chem 273: 33011-33019.
40. Dennler S, Itoh S, Vivien D, ten Dijke P, Huet S, et al. (1998) Direct binding of Smad3 and Smad4 to critical TGF beta-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene. Embo J 17: 3091-3100.
41. Santibanez JF, Letamendia A, Perez-Barriocanal F, Silvestri C, Saura M, et al. (2007) Endoglin increases eNOS expression by modulating Smad2 protein levels and Smad2-dependent TGF-beta signaling. J Cell Physiol 210: 456-468.
42. Korchynskyi O, ten Dijke P, (2002) Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter. J Biol Chem 277: 4883-4891.
43. Jerkic M, Rodriguez-Barbero A, Prieto M, Toporsian M, Pericacho M, et al. (2006) Reduced angiogenic responses in adult Endoglin heterozygous mice. Cardiovasc Res 69: 845-854.
44. Jerkic M, Rivas-Elena JV, Santibanez JF, Prieto M, Rodriguez-Barbero A, et al. (2006) Endoglin regulates cyclooxygenase-2 expression and activity. Circ Res 99: 248-256.
45. Blanco FJ, Santibanez JF, Guerrero-Esteo M, Langa C, Vary CP, et al. (2005) Interaction and functional interplay between endoglin and ALK-1, two components of the endothelial transforming growth factor-beta receptor complex. J Cell Physiol 204: 574-584.
46. David L, Mallet C, Mazerbourg S, Feige JJ, Bailly S, (2007) Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood 109: 1953-1961.
47. Koleva RI, Conley BA, Romero D, Riley KS, Marto JA, et al. (2006) Endoglin structure and function: Determinants of endoglin phosphorylation by transforming growth factor-beta receptors. J Biol Chem 281: 25110-25123.
48. Pece-Barbara N, Vera S, Kathirkamathamby K, Liebner S, Di Guglielmo GM, et al. (2005) Endoglin null endothelial cells proliferate faster and are more responsive to transforming growth factor beta1 with higher affinity receptors and an activated Alk1 pathway. J Biol Chem 280: 27800-27808.
49. Lee NY, Blobe GC, (2007) The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells. J Biol Chem 282: 21507-21517.
50. Rodriguez-Barbero A, Obreo J, Alvarez-Munoz P, Pandiella A, Bernabeu C, et al. (2006) Endoglin modulation of TGF-beta1-induced collagen synthesis is dependent on ERK1/2 MAPK activation. Cell Physiol Biochem 18: 135-142.
51. Scheid MP, Woodgett JR, (2003) Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Lett 546: 108-112.
52. Vlahos CJ, Matter WF, Hui KY, Brown RF, (1994) A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem 269: 5241-5248.
53. Collado M, Medema RH, Garcia-Cao I, Dubuisson ML, Barradas M, et al. (2000) Inhibition of the phosphoinositide 3-kinase pathway induces a senescence-like arrest mediated by p27Kip1. J Biol Chem 275: 21960-21968.
54. Kisseleva T, Brenner DA, (2008) Mechanisms of fibrogenesis. Exp Biol Med (Maywood) 233: 109-122.
55. Lam AP, Gottardi CJ, (2011) beta-catenin signaling: a novel mediator of fibrosis and potential therapeutic target. Curr Opin Rheumatol 23: 562-567.
56. McAnulty RJ, (2007) Fibroblasts and myofibroblasts: their source, function and role in disease. Int J Biochem Cell Biol 39: 666-671.
57. Torsney E, Charlton R, Parums D, Collis M, Arthur HM, (2002) Inducible expression of human endoglin during inflammation and wound healing in vivo. Inflamm Res 51: 464-470.
58. Duwel A, Eleno N, Jerkic M, Arevalo M, Bolanos JP, et al. (2007) Reduced tumor growth and angiogenesis in endoglin-haploinsufficient mice. Tumour Biol 28: 1-8.
59. Perez-Gomez E, Villa-Morales M, Santos J, Fernandez-Piqueras J, Gamallo C, et al. (2007) A role for endoglin as a suppressor of malignancy during mouse skin carcinogenesis. Cancer Res 67: 10268-10277.
60. Osaki M, Oshimura M, Ito H, (2004) PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9: 667-676.
61. Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, et al. (2004) PI3K/Akt signalling pathway and cancer. Cancer Treat Rev 30: 193-204.
62. Vivanco I, Sawyers CL, (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2: 489-501.
63. Feutz AC, Barrandon Y, Monard D, (2008) Control of thrombin signaling through PI3K is a mechanism underlying plasticity between hair follicle dermal sheath and papilla cells. J Cell Sci 121: 1435-1443.
64. Kapoor M, Liu S, Shi-wen X, Huh K, McCann M, et al. (2008) GSK-3beta in mouse fibroblasts controls wound healing and fibrosis through an endothelin-1-dependent mechanism. J Clin Invest 118: 3279-3290.
65. Sanz-Rodriguez F, Guerrero-Esteo M, Botella LM, Banville D, Vary CP, et al. (2004) Endoglin regulates cytoskeletal organization through binding to ZRP-1, a member of the Lim family of proteins. J Biol Chem 279: 32858-32868.
66. Toporsian M, Gros R, Kabir MG, Vera S, Govindaraju K, et al. (2005) A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res 96: 684-692.
67. Mouta-Bellum C, Kirov A, Miceli-Libby L, Mancini ML, Petrova TV, et al. (2009) Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85alpha, p55alpha, and p50alpha. Dev Dyn 238: 2670-2679.
68. Fujita D, Tanabe A, Sekijima T, Soen H, Narahara K, et al. (2010) Role of extracellular signal-regulated kinase and AKT cascades in regulating hypoxia-induced angiogenic factors produced by a trophoblast-derived cell line. J Endocrinol 206: 131-140.
69. Shyu KG, Wang BW, Chen WJ, Kuan P, Hung CR, (2010) Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-beta1 in cultured cardiac fibroblasts. Eur J Heart Fail 12: 219-226.
70. Cudmore MJ, Ahmad S, Sissaoui S, Ramma W, Ma B, et al. (2010) Loss of Akt activity increases circulating soluble endoglin release in preeclampsia: identification of inter-dependency between Akt-1 and heme oxygenase-1. Eur Heart J 33: 1150-1158.
71. Subramaniam V, Chakrabarti R, Prud'homme GJ, Jothy S, (2010) Tranilast inhibits cell proliferation and migration and promotes apoptosis in murine breast cancer. Anticancer Drugs 21: 351-361.
72. Lee NY, Golzio C, Gatza CE, Sharma A, Katsanis N, et al. (2012) Endoglin Regulates PI3-Kinase/Akt Trafficking and Signaling to Alter Endothelial Capillary Stability During Angiogenesis. Mol Biol Cell.