Inactivation of urokinase-type plasminogen activator receptor (uPAR) gene induces dermal and pulmonary fibrosis and peripheral microvasculopathy in mice: A new model of experimental scleroderma?

Annals of the Rheumatic Diseases

Volumn 73, Issue 9, 2014, Pages 1700-1709

  Manetti, Mirko ^a   Rosa, Irene ^a   Milia, Anna Franca ^a   Guiducci, Serena ^b   Carmeliet, Peter ^c,d   Ibba Manneschi, Lidia ^a   Matucci Cerinic, Marco ^b  

^a UNIVERSITY OF FLORENCE   (Italy)

^b CAREGGI UNIVERSITY HOSPITAL   (Italy)

^c DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^d UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

PULMONARY FIBROSIS; QUALITATIVE RESEARCH; SYSTEMIC SCLEROSIS;

ADULT; AGED; ANIMALS; APOPTOSIS; BIOPSY; COLLAGEN; CYTOKINES; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; ENDOTHELIUM, VASCULAR; FEMALE; FIBROSIS; HUMANS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROVESSELS; MIDDLE AGED; MYOFIBROBLASTS; PERIPHERAL VASCULAR DISEASES; PULMONARY FIBROSIS; RECEPTORS, UROKINASE PLASMINOGEN ACTIVATOR; SCLERODERMA, SYSTEMIC; SKIN;

EID: 84905158456     PISSN: 00034967     EISSN: 14682060     Source Type: Journal    
DOI: 10.1136/annrheumdis-2013-203706     Document Type: Article

References (46)

1. Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med 2009;360:1989-2003.
2. Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest 2007;117:557-67. (Pubitemid 46348510)
3. Manetti M, Guiducci S, Ibba-Manneschi L, et al. Mechanisms in the loss of capillaries in systemic sclerosis: angiogenesis versus vasculogenesis. J Cell Mol Med 2010;14:1241-54.
4. Bhattacharyya S, Wei J, Varga J. Understanding fibrosis in systemic sclerosis: shifting paradigms, emerging opportunities. Nat Rev Rheumatol 2011;8:42-54.
5. Tyndall AJ, Bannert B, Vonk M, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 2010;69:1809-15.
6. Ong VH, Denton CP. Innovative therapies for systemic sclerosis. Curr Opin Rheumatol 2010;22:264-72.
7. Manetti M, Neumann E, Distler O, et al. Animal models of scleroderma: from cellular and molecular mechanisms to novel antifibrotic strategies. In: Abraham D, Handler C, Dashwood M, Coghlan G, eds. Advances in vascular medicine. London: Springer-Verlag, 2010: 57-75.
8. Avouac J, Elhai M, Allanore Y. Experimental models of dermal fibrosis and systemic sclerosis. Joint Bone Spine 2013;80:23-8.
9. Maurer B, Busch N, Jüngel A, et al. Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis . Circulation 2009;120:2367-76.
10. Ragno P. The urokinase receptor: a ligand or a receptor? Story of a sociable molecule. Cell Mol Life Sci 2006;63:1028-37. (Pubitemid 43800773)
11. Mondino A, Resnati M, Blasi F. Structure and function of the urokinase receptor. Thromb Haemost 1999;82:19-22. (Pubitemid 30093625)
12. Zhao Y, Lyons CE Jr, Xiao A, et al . Urokinase directly activates matrix metalloproteinases-9: a potential role in glioblastoma invasion. Biochem Biophys Res Commun 2008;369:1215-20.
13. Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 2002;3:932-43. (Pubitemid 35477371)
14. D'Alessio S, Fibbi G, Cinelli M, et al. Matrix metalloproteinase 12-dependent cleavage of urokinase receptor in systemic sclerosis microvascular endothelial cells results in impaired angiogenesis. Arthritis Rheum 2004;50:3275-85.
15. Margheri F, Manetti M, Serrati S, et al. Domain 1 of the urokinase-type plasminogen activator receptor is required for its morphologic and functional, β2 integrin-mediated connection with actin cytoskeleton in human microvascular endothelial cells: failure of association in systemic sclerosis endothelial cells. Arthritis Rheum 2006;54:3926-38. (Pubitemid 44955896)
16. Poettler M, Unseld M, Mihaly-Bison J, et al. The urokinase receptor (CD87) represents a central mediator of growth factor-induced endothelial cell migration. Thromb Haemost 2012;108:357-66.
17. Alexander RA, Prager GW, Mihaly-Bison J, et al. VEGF-induced endothelial cell migration requires urokinase receptor (uPAR)-dependent integrin redistribution. Cardiovasc Res 2012;94:125-35.
18. Balsara RD, Merryman R, Virjee F, et al. A deficiency of uPAR alters endothelial angiogenic function and cell morphology. Vasc Cell 2011;3:10.
19. Zhang G, Kim H, Cai X, et al. Urokinase receptor deficiency accelerates renal fibrosis in obstructive nephropathy. J Am Soc Nephrol 2003;14:1254-71. (Pubitemid 36514666)
20. Kanno Y, Kaneiwa A, Minamida M, et al. The absence of uPAR is associated with the progression of dermal fibrosis. J Invest Dermatol 2008;128:2792-7.
21. Bernstein AM, Twining SS, Warejcka DJ, et al. Urokinase receptor cleavage: a crucial step in fibroblast-to-myofibroblast differentiation. Mol Biol Cell 2007;18:2716-27. (Pubitemid 47025736)
22. Hinz B, Phan SH, Thannickal VJ, et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol 2012;180:1340-55.
23. Milia AF, Del Rosso A, Pacini A, et al. Differential expression of tissue kallikrein in the skin of systemic sclerosis. Histol Histopathol 2005;20:415-22. (Pubitemid 40468261)
24. Manetti M, Guiducci S, Ruffo M, et al. Evidence for progressive reduction and loss of telocytes in the dermal cellular network of systemic sclerosis. J Cell Mol Med 2013;17:482-96.
25. Manetti M, Guiducci S, Romano E, et al. Differential expression of junctional adhesion molecules in different stages of systemic sclerosis. Arthritis Rheum 2013;65:247-57.
26. LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988;15:202-5. (Pubitemid 18073738)
27. Dewerchin M, Nuffelen AV, Wallays G, et al. Generation and characterization of urokinase receptor-deficient mice. J Clin Invest 1996;97:870-8. (Pubitemid 26057107)
28. Woessner JF Jr. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys 1961;93:440-7.
29. du Bois RM. Mechanisms of scleroderma-induced lung disease. Proc Am Thorac Soc 2007;4:434-8.
30. Beyer C, Distler O, Distler JH. Innovative antifibrotic therapies in systemic sclerosis. Curr Opin Rheumatol 2012;24:274-80.
31. Maurer B, Reich N, Juengel A, et al. Fra-2 transgenic mice as a novel model of pulmonary hypertension associated with systemic sclerosis. Ann Rheum Dis 2012;71:1382-7.
32. Stawski L, Han R, Bujor AM, et al. Angiotensin II induces skin fibrosis: a novel mouse model of dermal fibrosis. Arthritis Res Ther 2012;14:R194.
33. Thoua NM, Derrett-Smith EC, Khan K, et al. Gut fibrosis with altered colonic contractility in a mouse model of scleroderma. Rheumatology (Oxford) 2012;51:1989-98.
34. Montuori N, Visconte V, Rossi G, et al. Soluble and cleaved forms of the urokinase-receptor: degradation products or active molecules? Thromb Haemost 2005;93:192-8. (Pubitemid 40253721)
35. Montuori N, Carriero MV, Salzano S, et al . The cleavage of the urokinase receptor regulates its multiple functions. J Biol Chem 2002;277:46932-9. (Pubitemid 36159197)
36. Hinz B, Gabbiani G. Mechanisms of force generation and transmission by myofibroblasts. Curr Opin Biotechnol 2003;14:538-46. (Pubitemid 37298041)
37. Wang L, Pedroja BS, Meyers EE, et al. Degradation of internalized αvβ5 integrin is controlled by uPAR bound uPA: effect on β1 integrin activity and α-SMA stress fiber assembly. PLoS One 2012;7:e33915.
38. Margheri F, Serratì S, Lapucci A, et al. Modulation of the angiogenic phenotype of normal and systemic sclerosis endothelial cells by gain-loss of function of pentraxin 3 and matrix metalloproteinase 12. Arthritis Rheum 2010;62:2488-98.
39. Manetti M, Allanore Y, Revillod L, et al. A genetic variation located in the promoter region of the UPAR (CD87) gene is associated with the vascular complications of systemic sclerosis. Arthritis Rheum 2011;63:247-56.
40. Denton CP, Abraham DJ. Transforming growth factor-β and connective tissue growth factor: key cytokines in sclerodermia pathogenesis. Curr Opin Rheumatol 2001;13:505-11. (Pubitemid 33070969)
41. Varga J, Whitfield ML. Transforming growth factor-beta in systemic sclerosis (scleroderma). Front Biosci (Schol Ed) 2009;1:226-35.
42. Kahaleh MB. Endothelin, an endothelial-dependent vasoconstrictor in scleroderma: enhanced production and profibrotic action. Arthritis Rheum 1991;34:978-83.
43. Manetti M, Neumann E, Milia AF, et al . Severe fibrosis and increased expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients. Arthritis Rheum 2007;56:3442-7. (Pubitemid 47585440)
44. Leask A. The role of endothelin-1 signaling in the fibrosis observed in systemic sclerosis. Pharmacol Res 2011;63:502-3.
45. Sgonc R, Grulich M, Dietrich H, et al. Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma. J Clin Invest 1996;3:785-92. (Pubitemid 26349184)
46. Prager GW, Mihaly J, Brunner PM, et al. Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein. Blood 2009;113:1383-90.