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Rapamycin Inhibits Transforming Growth Factor β1-Induced Fibrogenesis in Primary Human Lung Fibroblasts
PURPOSE: The present study was designed to determine whether rapamycin could inhibit transforming growth factor β1 (TGF-β1)-induced fibrogenesis in primary lung fibroblasts, and whether the effect of inhibition would occur through the mammalian target of rapamycin (mTOR) and its downstream p70S6K pa...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Yonsei University College of Medicine
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576000/ https://www.ncbi.nlm.nih.gov/pubmed/23364979 http://dx.doi.org/10.3349/ymj.2013.54.2.437 |
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author | Gao, Yu Xu, Xuefeng Ding, Ke Liang, Yan Jiang, Dianhua Dai, Huaping |
author_facet | Gao, Yu Xu, Xuefeng Ding, Ke Liang, Yan Jiang, Dianhua Dai, Huaping |
author_sort | Gao, Yu |
collection | PubMed |
description | PURPOSE: The present study was designed to determine whether rapamycin could inhibit transforming growth factor β1 (TGF-β1)-induced fibrogenesis in primary lung fibroblasts, and whether the effect of inhibition would occur through the mammalian target of rapamycin (mTOR) and its downstream p70S6K pathway. MATERIALS AND METHODS: Primary normal human lung fibroblasts were obtained from histological normal lung tissue of 3 patients with primary spontaneous pneumothorax. Growth arrested, synchronized fibroblasts were treated with TGF-β1 (10 ng/mL) and different concentrations of rapamycin (0.01, 0.1, 1, 10 ng/mL) for 24 h. We assessed m-TOR, p-mTOR, S6K1, p-S6K1 by Western blot analysis, detected type III collagen and fibronectin secreting by ELISA assay, and determined type III collagen and fibronectin mRNA levels by real-time PCR assay. RESULTS: Rapamycin significantly reduced TGF-β1-induced type III collagen and fibronectin levels, as well as type III collagen and fibronectin mRNA levels. Furthermore, we also found that TGF-β1-induced mTOR and p70S6K phosphorylation were significantly down-regulated by rapamycin. The mTOR/p70S6K pathway was activated through the TGF-β1-mediated fibrogenic response in primary human lung fibroblasts. CONCLUSION: These results indicate that rapamycin effectively suppresses TGF-β1-induced type III collagen and fibronectin levels in primary human lung fibroblasts partly through the mTOR/p70S6K pathway. Rapamycin has a potential value in the treatment of pulmonary fibrosis. |
format | Online Article Text |
id | pubmed-3576000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Yonsei University College of Medicine |
record_format | MEDLINE/PubMed |
spelling | pubmed-35760002013-03-01 Rapamycin Inhibits Transforming Growth Factor β1-Induced Fibrogenesis in Primary Human Lung Fibroblasts Gao, Yu Xu, Xuefeng Ding, Ke Liang, Yan Jiang, Dianhua Dai, Huaping Yonsei Med J Original Article PURPOSE: The present study was designed to determine whether rapamycin could inhibit transforming growth factor β1 (TGF-β1)-induced fibrogenesis in primary lung fibroblasts, and whether the effect of inhibition would occur through the mammalian target of rapamycin (mTOR) and its downstream p70S6K pathway. MATERIALS AND METHODS: Primary normal human lung fibroblasts were obtained from histological normal lung tissue of 3 patients with primary spontaneous pneumothorax. Growth arrested, synchronized fibroblasts were treated with TGF-β1 (10 ng/mL) and different concentrations of rapamycin (0.01, 0.1, 1, 10 ng/mL) for 24 h. We assessed m-TOR, p-mTOR, S6K1, p-S6K1 by Western blot analysis, detected type III collagen and fibronectin secreting by ELISA assay, and determined type III collagen and fibronectin mRNA levels by real-time PCR assay. RESULTS: Rapamycin significantly reduced TGF-β1-induced type III collagen and fibronectin levels, as well as type III collagen and fibronectin mRNA levels. Furthermore, we also found that TGF-β1-induced mTOR and p70S6K phosphorylation were significantly down-regulated by rapamycin. The mTOR/p70S6K pathway was activated through the TGF-β1-mediated fibrogenic response in primary human lung fibroblasts. CONCLUSION: These results indicate that rapamycin effectively suppresses TGF-β1-induced type III collagen and fibronectin levels in primary human lung fibroblasts partly through the mTOR/p70S6K pathway. Rapamycin has a potential value in the treatment of pulmonary fibrosis. Yonsei University College of Medicine 2013-03-01 2013-01-22 /pmc/articles/PMC3576000/ /pubmed/23364979 http://dx.doi.org/10.3349/ymj.2013.54.2.437 Text en © Copyright: Yonsei University College of Medicine 2013 http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Gao, Yu Xu, Xuefeng Ding, Ke Liang, Yan Jiang, Dianhua Dai, Huaping Rapamycin Inhibits Transforming Growth Factor β1-Induced Fibrogenesis in Primary Human Lung Fibroblasts |
title | Rapamycin Inhibits Transforming Growth Factor β1-Induced Fibrogenesis in Primary Human Lung Fibroblasts |
title_full | Rapamycin Inhibits Transforming Growth Factor β1-Induced Fibrogenesis in Primary Human Lung Fibroblasts |
title_fullStr | Rapamycin Inhibits Transforming Growth Factor β1-Induced Fibrogenesis in Primary Human Lung Fibroblasts |
title_full_unstemmed | Rapamycin Inhibits Transforming Growth Factor β1-Induced Fibrogenesis in Primary Human Lung Fibroblasts |
title_short | Rapamycin Inhibits Transforming Growth Factor β1-Induced Fibrogenesis in Primary Human Lung Fibroblasts |
title_sort | rapamycin inhibits transforming growth factor β1-induced fibrogenesis in primary human lung fibroblasts |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576000/ https://www.ncbi.nlm.nih.gov/pubmed/23364979 http://dx.doi.org/10.3349/ymj.2013.54.2.437 |
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