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Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages

Radiation-induced lung fibrosis (RILF) is a common side effect for patients with thoracic cancer receiving radiation therapy. RILF is characterized by excessive collagen deposition mediated by TGF-β1 and its downstream factor SMAD3, but the exact molecular mechanism leading to fibrosis is yet to be...

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Autores principales: Duru, Nadire, Zhang, Yongshu, Gernapudi, Ramkishore, Wolfson, Benjamin, Lo, Pang-Kuo, Yao, Yuan, Zhou, Qun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5172237/
https://www.ncbi.nlm.nih.gov/pubmed/27996039
http://dx.doi.org/10.1038/srep39572
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author Duru, Nadire
Zhang, Yongshu
Gernapudi, Ramkishore
Wolfson, Benjamin
Lo, Pang-Kuo
Yao, Yuan
Zhou, Qun
author_facet Duru, Nadire
Zhang, Yongshu
Gernapudi, Ramkishore
Wolfson, Benjamin
Lo, Pang-Kuo
Yao, Yuan
Zhou, Qun
author_sort Duru, Nadire
collection PubMed
description Radiation-induced lung fibrosis (RILF) is a common side effect for patients with thoracic cancer receiving radiation therapy. RILF is characterized by excessive collagen deposition mediated by TGF-β1 and its downstream factor SMAD3, but the exact molecular mechanism leading to fibrosis is yet to be determined. The present study investigated the impact of miR-140 on RILF development. Herein, we first found that loss of miR-140 is a marker of fibrotic lung tissue in vivo one-year post-radiation treatment. We showed that miR-140 knockout primary lung fibroblasts have a higher percentage of myofibroblasts compared to wild type primary lung fibroblasts, and that loss of miR-140 expression leads to increased activation of TGF-β1 signaling as well as increased myofibroblast differentiation. We also identified fibronectin as a novel miR-140 target gene in lung fibroblasts. Finally, we have shown that miR-140 deficiency promotes accumulation of M2 macrophages in irradiated lung tissues. These data suggest that miR-140 is a key protective molecule against RILF through inhibiting myofibroblast differentiation and inflammation.
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spelling pubmed-51722372016-12-28 Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages Duru, Nadire Zhang, Yongshu Gernapudi, Ramkishore Wolfson, Benjamin Lo, Pang-Kuo Yao, Yuan Zhou, Qun Sci Rep Article Radiation-induced lung fibrosis (RILF) is a common side effect for patients with thoracic cancer receiving radiation therapy. RILF is characterized by excessive collagen deposition mediated by TGF-β1 and its downstream factor SMAD3, but the exact molecular mechanism leading to fibrosis is yet to be determined. The present study investigated the impact of miR-140 on RILF development. Herein, we first found that loss of miR-140 is a marker of fibrotic lung tissue in vivo one-year post-radiation treatment. We showed that miR-140 knockout primary lung fibroblasts have a higher percentage of myofibroblasts compared to wild type primary lung fibroblasts, and that loss of miR-140 expression leads to increased activation of TGF-β1 signaling as well as increased myofibroblast differentiation. We also identified fibronectin as a novel miR-140 target gene in lung fibroblasts. Finally, we have shown that miR-140 deficiency promotes accumulation of M2 macrophages in irradiated lung tissues. These data suggest that miR-140 is a key protective molecule against RILF through inhibiting myofibroblast differentiation and inflammation. Nature Publishing Group 2016-12-20 /pmc/articles/PMC5172237/ /pubmed/27996039 http://dx.doi.org/10.1038/srep39572 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Duru, Nadire
Zhang, Yongshu
Gernapudi, Ramkishore
Wolfson, Benjamin
Lo, Pang-Kuo
Yao, Yuan
Zhou, Qun
Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages
title Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages
title_full Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages
title_fullStr Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages
title_full_unstemmed Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages
title_short Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages
title_sort loss of mir-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5172237/
https://www.ncbi.nlm.nih.gov/pubmed/27996039
http://dx.doi.org/10.1038/srep39572
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