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Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in macrophages
Idiopathic pulmonary fibrosis is a progressive interstitial pneumonia characterised by fibroblast accumulation, collagen deposition and extracellular matrix (ECM) remodelling. It was reported that Akt1 mediated idiopathic pulmonary fibrosis progression through regulating the apoptosis of alveolar ma...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900639/ https://www.ncbi.nlm.nih.gov/pubmed/31299858 http://dx.doi.org/10.1177/1753425919861774 |
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author | Nie, Yunjuan Hu, Yudong Yu, Kaikai Zhang, Dan Shi, Yinze Li, Yaolin Sun, Lei Qian, Feng |
author_facet | Nie, Yunjuan Hu, Yudong Yu, Kaikai Zhang, Dan Shi, Yinze Li, Yaolin Sun, Lei Qian, Feng |
author_sort | Nie, Yunjuan |
collection | PubMed |
description | Idiopathic pulmonary fibrosis is a progressive interstitial pneumonia characterised by fibroblast accumulation, collagen deposition and extracellular matrix (ECM) remodelling. It was reported that Akt1 mediated idiopathic pulmonary fibrosis progression through regulating the apoptosis of alveolar macrophage, while its effect on macrophage-produced cytokines remains largely unknown. In the present study, we first examined the phosphorylation of Akt1 in lung sections from idiopathic pulmonary fibrosis patients by immunohistochemistry before applying a bleomycin-induced idiopathic pulmonary fibrosis model using Akt1(−/−) mice and Akt1(+/+) littermates. The results showed that Akt1 was remarkably up-regulated in idiopathic pulmonary fibrosis patients, while in vivo studies revealed that Akt1-deficient mice had well-preserved alveolar structure and fewer collagens, secreted fewer matrix components, including alpha smooth-muscle actin and fibronectin and survived significantly longer than Akt1(+/+) littermates. Additionally, the pro-fibrogenic cytokine IL-13 was down-regulated at least twofold in Akt1(−/−)mice compared to the Akt1(+/+)group on d 3 and 7 after bleomycin treatment. Furthermore, it was found that Akt1(–/–) macrophages displayed down-regulation of IL-13 compared to Akt1(+/+) macrophages in which Akt1 was phosphorylated in response to IL-33 stimulation. These findings indicate that Akt1 modulates pulmonary fibrosis through inducing IL-13 production by macrophages, suggesting that targeting Akt1 may simultaneously block the fibrogenic processes of idiopathic pulmonary fibrosis. |
format | Online Article Text |
id | pubmed-6900639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-69006392019-12-13 Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in macrophages Nie, Yunjuan Hu, Yudong Yu, Kaikai Zhang, Dan Shi, Yinze Li, Yaolin Sun, Lei Qian, Feng Innate Immun Original Articles Idiopathic pulmonary fibrosis is a progressive interstitial pneumonia characterised by fibroblast accumulation, collagen deposition and extracellular matrix (ECM) remodelling. It was reported that Akt1 mediated idiopathic pulmonary fibrosis progression through regulating the apoptosis of alveolar macrophage, while its effect on macrophage-produced cytokines remains largely unknown. In the present study, we first examined the phosphorylation of Akt1 in lung sections from idiopathic pulmonary fibrosis patients by immunohistochemistry before applying a bleomycin-induced idiopathic pulmonary fibrosis model using Akt1(−/−) mice and Akt1(+/+) littermates. The results showed that Akt1 was remarkably up-regulated in idiopathic pulmonary fibrosis patients, while in vivo studies revealed that Akt1-deficient mice had well-preserved alveolar structure and fewer collagens, secreted fewer matrix components, including alpha smooth-muscle actin and fibronectin and survived significantly longer than Akt1(+/+) littermates. Additionally, the pro-fibrogenic cytokine IL-13 was down-regulated at least twofold in Akt1(−/−)mice compared to the Akt1(+/+)group on d 3 and 7 after bleomycin treatment. Furthermore, it was found that Akt1(–/–) macrophages displayed down-regulation of IL-13 compared to Akt1(+/+) macrophages in which Akt1 was phosphorylated in response to IL-33 stimulation. These findings indicate that Akt1 modulates pulmonary fibrosis through inducing IL-13 production by macrophages, suggesting that targeting Akt1 may simultaneously block the fibrogenic processes of idiopathic pulmonary fibrosis. SAGE Publications 2019-07-12 2019-10 /pmc/articles/PMC6900639/ /pubmed/31299858 http://dx.doi.org/10.1177/1753425919861774 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Articles Nie, Yunjuan Hu, Yudong Yu, Kaikai Zhang, Dan Shi, Yinze Li, Yaolin Sun, Lei Qian, Feng Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in macrophages |
title | Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in
macrophages |
title_full | Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in
macrophages |
title_fullStr | Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in
macrophages |
title_full_unstemmed | Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in
macrophages |
title_short | Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in
macrophages |
title_sort | akt1 regulates pulmonary fibrosis via modulating il-13 expression in
macrophages |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900639/ https://www.ncbi.nlm.nih.gov/pubmed/31299858 http://dx.doi.org/10.1177/1753425919861774 |
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