Thrombin-induced CCN2 expression as a target for anti-fibrotic therapy in scleroderma

Journal of Cell Communication and Signaling

Volumn 4, Issue 2, 2010, Pages 111-112

  Leask, Andrew ^a  

^a WESTERN UNIVERSITY   (Canada)

Author keywords

CCN2; CTGF; Fibrosis; Myofiroblast; Scleroderma; Thrombin

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; ANTIFIBROTIC AGENT; CONNECTIVE TISSUE GROWTH FACTOR; DABIGATRAN; THROMBIN; TRANSFORMING GROWTH FACTOR BETA;

ARTICLE; CELL DIFFERENTIATION; DRUG PROTEIN BINDING; FIBROSIS; MYOFIBROBLAST; PRIORITY JOURNAL; PROTEIN EXPRESSION; SCLERODERMA;

RHEUM;

EID: 77954689151     PISSN: 18739601     EISSN: 1873961X     Source Type: Journal    
DOI: 10.1007/s12079-009-0082-2     Document Type: Article

References (16)

1. Bogatkevich GS, Tourkina E, Silver RM, Ludwicka-Bradley A (2001) Thrombin differentiates normal lung fibroblasts to a myofibroblast phenotype via proteolytically activated receptor-1 and protein kinase C-dependent pathway. J Biol Chem 276:45184-45192
2. Bogatkevich GS, Ludwicka-Bradley A, Silver RM (2009) Dabigatran, a direct thrombin inhibitor, demonstrates antifibrotic effects on lung fibroblasts. Arthritis Rheum 60:3455-3464
3. Chambers RC, Leoni P, Blanc-Brude OP, Wembridge DE, Laurent GJ (2000) Thrombin is a potent inducer of connective tissue growth factor production via proteolytic activation of protease-activated receptor-1. J Biol Chem 275:35584-35591
4. Chen Y, Shiwen X, van Beek J, Kennedy L, McLeod M, Renzoni EA, Bou-Gharios G, Wilcox-Adelman S, Goetinck PF, Eastwood M, Black CM, Abraham DJ, Leask A (2005) Matrix contraction by dermal fibroblasts requires TGFbeta/ALK5, heparan sulfate containing proteoglycans and MEK/ERK: insights into pathological scarring in chronic fibrotic disease. Am J Pathol 167:1699-1711
5. Chen Y, Shi-wen X, Eastwood M, Black CM, Denton CP, Leask A, Abraham DJ (2006) ALK5 (TGFB receptor type I) signaling contributes to the fibrotic phenotype of scleroderma fibroblasts. Arthritis Rheum 54:1309-1316
6. Dziadzio M, Usinger W, Leask A, Abraham D, Black CM, Denton D, Stratton R (2005) N-terminal CTGF is marker of fibrosis for the connective tissue disease scleroderma. QJM 98:485-492
7. Green D (2006) Coagulation cascade. Hemodial Int 10(Suppl 2):S2-S4
8. Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G (2007) The myofibroblast: one function, multiple origins. Am J Pathol 170:1807-1816
9. Leask A (2004) Transcriptional profiling of the scleroderma fibroblast reveals a role for CTGF in fibrosis. Keio J Med 53:74-77
10. Leask A (2006) Scar wars: is TGF| the phantom menace in scleroderma? Arthritis Res Ther 8(4):213
11. Leask A, Parapuram SK, Shiwen X, Abraham DJ (2009) Connective tissue growth factor (CTGF, CCN2) gene expression: a potent clinical marker of fibroproliferative disease. J Cell Commun Signal 3:89-94
12. Lepailleur-Enouf D, Valdenaire O, Philippe M, Jandrot-Perrus M, Michel JB (2000) (2000) Thrombin induces endothelin expression in arterial smooth muscle cells. Am J Physiol Heart Circ Physiol 278:H1606-H1612
13. Shiwen X, Chen Y, Denton CP, Eastwood M, Renzoni E, Bou-Gharios G, Dashwood MR, duBois R, Black CM, Leask A, Abraham DJ (2004) Endothelin-1 promotes mechanoregulation and myofibro- blast formation in fibroblasts through the ETA receptor via Akt/ PI3 kinase: implications for lung fibrosis. Mol Biol Cell 15:2707-2719
14. Shi-wen X, Renzoni EA, Kennedy L, Howat S, Chen Y, Pearson JD, Bou-Gharios G, Dashwood MR, du Bois RM, Black CM, Denton CP, Abraham DJ, Leask A (2007) Endogenous endothelin-1 signaling contributes to type I collagen and CCN2 over- expression in fibrotic fibroblasts. Matrix Biol 26:625-632
15. Sorbera LA, Bozza J, Castaner J (2005) Dabigatran/Dabigatran etexilate prevention of DVT, prevention of ischemic stroke, thrombin inhibitor. Drugs Future 30:877-885
16. Varga J, Abraham D (2007) Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest 117:557-567