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...
| Hoofdauteurs: | , , , , , , , , |
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| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
2007
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| _version_ | 1826268886170861568 |
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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. |
| first_indexed | 2024-03-06T21:16:27Z |
| format | Journal article |
| id | oxford-uuid:3ff229b1-0dd7-4bfb-9a1d-f8812a04d1d7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:16:27Z |
| publishDate | 2007 |
| record_format | dspace |
| 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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