单位：[1]The Center for Biomedical Research, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.华中科技大学同济医学院附属同济医院生物医学研究中心科研平台[2]Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, 1095 Jiefang Ave, Wuhan 430030, China.[3]Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Guilin Medical University, 212 Renmin Road, Guilin 541000, China[4]Department of Respiratory Medicine, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Lu, Shanghai, 200011, China.
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-beta 1 (TGF-beta 1) 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, intra-tracheal 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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81530024, 91749207, 81920108009, 81770823, 81800068, 81670729]; Ministry of Science and Technology [2016YFC1305002, 2017YFC1309603]; NHC Drug Discovery Program [2017ZX09304022-07]; Department of Science and Technology of Hubei State [2017ACA096]; Integrated Innovative Team for Major Human Disease Programs of Tongji Medical College, and Huazhong University of Science and Technology
第一作者单位：[1]The Center for Biomedical Research, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.[2]Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, 1095 Jiefang Ave, Wuhan 430030, China.
共同第一作者：
通讯作者：
通讯机构：[1]The Center for Biomedical Research, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.[3]Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Guilin Medical University, 212 Renmin Road, Guilin 541000, China
推荐引用方式(GB/T 7714)：
Wang Yi,Zhang Lei,Wu Guo-Rao,et al.MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program[J].SCIENCE ADVANCES.2021,7(1):doi:10.1126/sciadv.abb6075.
APA：
Wang, Yi,Zhang, Lei,Wu, Guo-Rao,Zhou, Qing,Yue, Huihui...&Wang, Cong-Yi.(2021).MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program.SCIENCE ADVANCES,7,(1)
MLA：
Wang, Yi,et al."MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program".SCIENCE ADVANCES 7..1(2021)
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