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MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program
Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis–associated interstitial lung disease, and id...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775789/ https://www.ncbi.nlm.nih.gov/pubmed/33277324 http://dx.doi.org/10.1126/sciadv.abb6075 |
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author | Wang, Yi Zhang, Lei Wu, Guo-Rao Zhou, Qing Yue, Huihui Rao, Li-Zong Yuan, Ting Mo, Biwen Wang, Fa-Xi Chen, Long-Min Sun, Fei Song, Jia Xiong, Fei Zhang, Shu Yu, Qilin Yang, Ping Xu, Yongjian Zhao, Jianping Zhang, Huilan Xiong, Weining Wang, Cong-Yi |
author_facet | Wang, Yi Zhang, Lei Wu, Guo-Rao Zhou, Qing Yue, Huihui Rao, Li-Zong Yuan, Ting Mo, Biwen Wang, Fa-Xi Chen, Long-Min Sun, Fei Song, Jia Xiong, Fei Zhang, Shu Yu, Qilin Yang, Ping Xu, Yongjian Zhao, Jianping Zhang, Huilan Xiong, Weining Wang, Cong-Yi |
author_sort | Wang, Yi |
collection | PubMed |
description | Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis–associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)–induced PF are characterized by the altered methyl-CpG–binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor–β1 (TGF-β1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings. |
format | Online Article Text |
id | pubmed-7775789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-77757892021-01-14 MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program Wang, Yi Zhang, Lei Wu, Guo-Rao Zhou, Qing Yue, Huihui Rao, Li-Zong Yuan, Ting Mo, Biwen Wang, Fa-Xi Chen, Long-Min Sun, Fei Song, Jia Xiong, Fei Zhang, Shu Yu, Qilin Yang, Ping Xu, Yongjian Zhao, Jianping Zhang, Huilan Xiong, Weining Wang, Cong-Yi Sci Adv Research Articles Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis–associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)–induced PF are characterized by the altered methyl-CpG–binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor–β1 (TGF-β1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings. American Association for the Advancement of Science 2021-01-01 /pmc/articles/PMC7775789/ /pubmed/33277324 http://dx.doi.org/10.1126/sciadv.abb6075 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Wang, Yi Zhang, Lei Wu, Guo-Rao Zhou, Qing Yue, Huihui Rao, Li-Zong Yuan, Ting Mo, Biwen Wang, Fa-Xi Chen, Long-Min Sun, Fei Song, Jia Xiong, Fei Zhang, Shu Yu, Qilin Yang, Ping Xu, Yongjian Zhao, Jianping Zhang, Huilan Xiong, Weining Wang, Cong-Yi MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program |
title | MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program |
title_full | MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program |
title_fullStr | MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program |
title_full_unstemmed | MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program |
title_short | MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program |
title_sort | mbd2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage m2 program |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775789/ https://www.ncbi.nlm.nih.gov/pubmed/33277324 http://dx.doi.org/10.1126/sciadv.abb6075 |
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