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

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 gro...

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Glavni autori: Shi-wen, X, Kennedy, L, Renzoni, E, Bou-Gharios, G, du Bois, R, Black, C, Denton, C, Abraham, D, Leask, A
Format: Journal article
Jezik:English
Izdano: 2007
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author Shi-wen, X
Kennedy, L
Renzoni, E
Bou-Gharios, G
du Bois, R
Black, C
Denton, C
Abraham, D
Leask, A
author_facet Shi-wen, X
Kennedy, L
Renzoni, E
Bou-Gharios, G
du Bois, R
Black, C
Denton, C
Abraham, D
Leask, A
author_sort Shi-wen, X
collection OXFORD
description 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 (TGFbeta) 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 TGFbeta in lung fibroblasts. METHODS: We used a specific endothelin receptor antagonist to determine whether ET-1 is a downstream mediator of TGFbeta responses in lung fibroblasts, using microarray technology, real-time polymerase chain reaction, and Western blot analyses. RESULTS: The ability of TGFbeta 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 TGFbeta 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.
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spelling oxford-uuid:3ff229b1-0dd7-4bfb-9a1d-f8812a04d1d72022-03-26T14:35:01ZEndothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3ff229b1-0dd7-4bfb-9a1d-f8812a04d1d7EnglishSymplectic Elements at Oxford2007Shi-wen, XKennedy, LRenzoni, EBou-Gharios, Gdu Bois, RBlack, CDenton, CAbraham, DLeask, A 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 (TGFbeta) 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 TGFbeta in lung fibroblasts. METHODS: We used a specific endothelin receptor antagonist to determine whether ET-1 is a downstream mediator of TGFbeta responses in lung fibroblasts, using microarray technology, real-time polymerase chain reaction, and Western blot analyses. RESULTS: The ability of TGFbeta 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 TGFbeta 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.
spellingShingle Shi-wen, X
Kennedy, L
Renzoni, E
Bou-Gharios, G
du Bois, R
Black, C
Denton, C
Abraham, D
Leask, A
Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts.
title Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts.
title_full Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts.
title_fullStr Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts.
title_full_unstemmed Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts.
title_short Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts.
title_sort endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts
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