PT  - JOURNAL ARTICLE
AU  - Wang, Yi
AU  - Zhang, Lei
AU  - Wu, Guo-Rao
AU  - Zhou, Qing
AU  - Yue, Huihui
AU  - Rao, Li-Zong
AU  - Yuan, Ting
AU  - Mo, Biwen
AU  - Wang, Fa-Xi
AU  - Chen, Long-Min
AU  - Sun, Fei
AU  - Song, Jia
AU  - Xiong, Fei
AU  - Zhang, Shu
AU  - Yu, Qilin
AU  - Yang, Ping
AU  - Xu, Yongjian
AU  - Zhao, Jianping
AU  - Zhang, Huilan
AU  - Xiong, Weining
AU  - Wang, Cong-Yi
TI  - MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program
AID  - 10.1126/sciadv.abb6075
DP  - 2021 Jan 01
TA  - Science Advances
PG  - eabb6075
VI  - 7
IP  - 1
4099  - http://advances.sciencemag.org/content/7/1/eabb6075.short
4100  - http://advances.sciencemag.org/content/7/1/eabb6075.full
SO  - Sci Adv2021 Jan 01; 7
AB  - 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.