期刊
SCIENCE ADVANCES
卷 7, 期 1, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb6075
关键词
-
资金
- National Natural Science Foundation of China [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
Despite extensive studies, the mechanisms underlying PF remain poorly understood. This study found altered MBD2 expression in macrophages in lungs from different types of PF patients and mice with PF, and Mbd2 deficiency protected against BLM-induced PF. Mbd2 selectively influenced TGF-β1 production and M2 macrophage program through Ship promoter binding in macrophages.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据