MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program

被引：194

作者：

Wang, Yi ^{[1
]}

Zhang, Lei ^{[1
]}

Wu, Guo-Rao ^{[1
]}

Zhou, Qing ^{[1
]}

Yue, Huihui ^{[1
]}

Rao, Li-Zong ^{[1
,2
]}

Yuan, Ting ^{[1
,2
]}

Mo, Biwen ^{[2
]}

Wang, Fa-Xi ^{[1
]}

Chen, Long-Min ^{[1
]}

Sun, Fei ^{[1
]}

Song, Jia ^{[1
]}

Xiong, Fei ^{[1
]}

Zhang, Shu ^{[1
]}

Yu, Qilin ^{[1
]}

Yang, Ping ^{[1
]}

Xu, Yongjian ^{[1
]}

Zhao, Jianping ^{[1
]}

Zhang, Huilan ^{[1
]}

Xiong, Weining ^{[1
,3
]}

Wang, Cong-Yi ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Ctr Biomed Res,NHC Key Lab Resp Dis,Dept Resp & C, 1095 Jiefang Ave, Wuhan 430030, Peoples R China

[2] Guilin Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 2, 212 Renmin Rd, Guilin 541000, Peoples R China

[3] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Resp Med, Sch Med, 639 Zhizaoju Lu, Shanghai 200011, Peoples R China

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 01期

基金：

中国国家自然科学基金;

关键词：

PROTECTS MICE; DNA METHYLATION; EXPRESSION; DIFFERENTIATION; INFLAMMATION; CORONAVIRUS; HOMEOSTASIS; RESISTANCE; CELLS; SHIP;

D O I：

10.1126/sciadv.abb6075

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

共 54 条

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