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Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts

Xu, SW; Kennedy, L; Renzoni, EA; Bou-Gharios, G; du Bois, RM; Black, CM; Denton, CP; ... Leask, A; + view all (2007) Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts. ARTHRITIS RHEUM , 56 (12) 4189 - 4194. 10.1002/art.23134.

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Abstract

Objective. Fibrosis is excessive scarring caused by the accumulation and contraction of extracellular matrix proteins and is a common end pathway in many chronic diseases, including scleroderma (systemic sclerosis [SSc]). Indeed, pulmonary fibrosis is a major cause of death in SSc. Transforming growth factor beta (TGF beta) induces endothelin 1 (ET-1) in human lung fibroblasts by a Smad-independent, JNK-dependent mechanism. The goal of this study was to assess whether ET-1 is a downstream mediator of the profibrotic effects of TGF beta in lung fibroblasts.Methods.. We used a specific endothelin receptor antagonist to determine whether ET-1 is a downstream mediator of TGF beta responses in lung fibroblasts, using microarray technology, real-time polymerase chain reaction, and Western blot analyses.Results. The ability of TGF beta to induce the expression of a cohort of profibrotic genes, including type I collagen, fibronectin, and CCN2, and to contract a collagen gel matrix, depends on ET-1.Conclusion. ET-1 contributes to the ability of TGF beta to promote a profibrotic phenotype in human lung fibroblasts, consistent with the notion that endothelin receptor antagonism may be beneficial in controlling fibrogenic responses in lung fibroblasts.

Type: Article
Title: Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts
DOI: 10.1002/art.23134
Keywords: TGF-BETA, SYSTEMIC-SCLEROSIS, FIBROSIS, SCLERODERMA, EXPRESSION, PHENOTYPE, KINASE-5, DISEASE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/78350
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