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N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma

Dziadzio, M; Usinger, W; Leask, A; Abraham, D; Black, CM; Denton, C; Stratton, R; (2005) N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma. QJM-INT J MED , 98 (7) 485 - 492. 10.1093/qjmed/hci078.

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Abstract

Background: Over-expression of connective tissue growth factor (CTGF) is a hallmark of fibrotic disease, including scleroderma. CTGF acts with the pro-fibrotic cytokine TGF beta to promote sustained fibrotic responses in vivo. Elevated production of CTGF might be responsible for maintenance of the fibrotic phenotype in scleroderma. Assays of CTGF or of its fragments are potential non-invasive measures of the fibrotic response in scleroderma.Aim: To determine the utility of whole, N-terminal, and C-terminal CTGF as surrogate markers for fibrosis in scleroderma.Design: Cross-sectional controlled study.Methods: Plasma was collected prospectively from 47 scleroderma patients (26 diffuse scleroderma, 21 limited scleroderma) and 18 healthy controls. At the same time, dermal interstitial fluid was derived by a suction blister technique from the lesional skin of scleroderma patients, and from the forearm skin of healthy controls. Whole, N-terminal, and C-terminal CTGF were assayed by ELISA, using monoclonal antibodies specific for N- and C-terminal epitopes.Results: N-terminal cleavage products of CTGF were present at elevated levels in the plasma and dermal interstitial fluid of scleroderma patients, compared to healthy controls. N-terminal CTGF levels in plasma and dermal interstitial fluid correlated with severity of skin disease and (negatively) with disease duration. Whole and C-terminal CTGF levels were low in blister fluid and plasma levels were not elevated in disease.Discussion: These results support a role for CTGF in scleroderma-associated fibrosis and the utility of N-terminal CTGF as a marker of fibrosis.

Type: Article
Title: N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma
DOI: 10.1093/qjmed/hci078
Keywords: FACTOR GENE-EXPRESSION, SYSTEMIC-SCLEROSIS, SKIN SCLEROSIS, TGF-BETA, FIBROSIS, CTGF, ASSOCIATION, REGULATORS, SECTIONS, DIFFUSE
URI: http://discovery.ucl.ac.uk/id/eprint/407253
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