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Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System
The exact molecular mechanism that mediates hypoxia-induced pulmonary fibrosis needs to be further clarified. The aim of this study was to explore the effect and underlying mechanism of angiotensin II (Ang II) on collagen synthesis in hypoxic human lung fibroblast (HLF) cells. The HLF-1 cell line wa...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Molecular Diversity Preservation International (MDPI)
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876092/ https://www.ncbi.nlm.nih.gov/pubmed/24336063 http://dx.doi.org/10.3390/ijms141224029 |
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author | Liu, Shan-Shan Wang, Hao-Yan Tang, Jun-Ming Zhou, Xiu-Mei |
author_facet | Liu, Shan-Shan Wang, Hao-Yan Tang, Jun-Ming Zhou, Xiu-Mei |
author_sort | Liu, Shan-Shan |
collection | PubMed |
description | The exact molecular mechanism that mediates hypoxia-induced pulmonary fibrosis needs to be further clarified. The aim of this study was to explore the effect and underlying mechanism of angiotensin II (Ang II) on collagen synthesis in hypoxic human lung fibroblast (HLF) cells. The HLF-1 cell line was used for in vitro studies. Angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression levels in human lung fibroblasts were analysed using real-time polymerase chain reaction (RT-PCR) after hypoxic treatment. Additionally, the collagen type I (Col-I), AT1R and nuclear factor κappaB (NF-κB) protein expression levels were detected using Western blot analysis, and NF-κB nuclear translocation was measured using immunofluorescence localization analysis. Ang II levels in HLF-1 cells were measured with an enzyme-linked immunosorbent assay (ELISA). We found that hypoxia increased Col-I mRNA and protein expression in HLF-1 cells, and this effect could be inhibited by an AT1R or AT2R inhibitor. The levels of NF-κB, RAS components and Ang II production in HLF-1 cells were significantly increased after the hypoxia exposure. Hypoxia or Ang II increased NF-κB-p50 protein expression in HLF-1 cells, and the special effect could be inhibited by telmisartan (TST), an AT1R inhibitor, and partially inhibited by PD123319, an AT2R inhibitor. Importantly, hypoxia-induced NF-κB nuclear translocation could be nearly completely inhibited by an AT1R or AT2R inhibitor. Furthermore pyrrolidine dithiocarbamate (PDTC), a NF-κB blocker, abolished the expression of hypoxia-induced AT1R and Col-I in HLF-1 cells. Our results indicate that Ang II-mediated NF-κB signalling via ATR is involved in hypoxia-induced collagen synthesis in human lung fibroblasts. |
format | Online Article Text |
id | pubmed-3876092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-38760922013-12-31 Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System Liu, Shan-Shan Wang, Hao-Yan Tang, Jun-Ming Zhou, Xiu-Mei Int J Mol Sci Article The exact molecular mechanism that mediates hypoxia-induced pulmonary fibrosis needs to be further clarified. The aim of this study was to explore the effect and underlying mechanism of angiotensin II (Ang II) on collagen synthesis in hypoxic human lung fibroblast (HLF) cells. The HLF-1 cell line was used for in vitro studies. Angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression levels in human lung fibroblasts were analysed using real-time polymerase chain reaction (RT-PCR) after hypoxic treatment. Additionally, the collagen type I (Col-I), AT1R and nuclear factor κappaB (NF-κB) protein expression levels were detected using Western blot analysis, and NF-κB nuclear translocation was measured using immunofluorescence localization analysis. Ang II levels in HLF-1 cells were measured with an enzyme-linked immunosorbent assay (ELISA). We found that hypoxia increased Col-I mRNA and protein expression in HLF-1 cells, and this effect could be inhibited by an AT1R or AT2R inhibitor. The levels of NF-κB, RAS components and Ang II production in HLF-1 cells were significantly increased after the hypoxia exposure. Hypoxia or Ang II increased NF-κB-p50 protein expression in HLF-1 cells, and the special effect could be inhibited by telmisartan (TST), an AT1R inhibitor, and partially inhibited by PD123319, an AT2R inhibitor. Importantly, hypoxia-induced NF-κB nuclear translocation could be nearly completely inhibited by an AT1R or AT2R inhibitor. Furthermore pyrrolidine dithiocarbamate (PDTC), a NF-κB blocker, abolished the expression of hypoxia-induced AT1R and Col-I in HLF-1 cells. Our results indicate that Ang II-mediated NF-κB signalling via ATR is involved in hypoxia-induced collagen synthesis in human lung fibroblasts. Molecular Diversity Preservation International (MDPI) 2013-12-10 /pmc/articles/PMC3876092/ /pubmed/24336063 http://dx.doi.org/10.3390/ijms141224029 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Liu, Shan-Shan Wang, Hao-Yan Tang, Jun-Ming Zhou, Xiu-Mei Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System |
title | Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System |
title_full | Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System |
title_fullStr | Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System |
title_full_unstemmed | Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System |
title_short | Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System |
title_sort | hypoxia-induced collagen synthesis of human lung fibroblasts by activating the angiotensin system |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876092/ https://www.ncbi.nlm.nih.gov/pubmed/24336063 http://dx.doi.org/10.3390/ijms141224029 |
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