中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Roxithromycin attenuates bleomycin-induced pulmonary fibrosis by targeting senescent cells

文献类型：期刊论文

作者Zhang, Xuan2,3; Dong, Ying2,3; Li, Wan-chen2,3; Tang, Bi-xi2,4; Li, Jia1,2,3,5; Zang, Yi2,3,5
刊名ACTA PHARMACOLOGICA SINICA
出版日期2021-03-02
页码11
关键词idiopathic pulmonary fibrosis cellular senescence roxithromycin NOX4 senescence-associated secretory phenotype (SASP)
ISSN号1671-4083
DOI10.1038/s41401-021-00618-3
通讯作者Li, Jia(Jli@simm.ac.cn) ; Zang, Yi(Yzang@simm.ac.cn)
英文摘要Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease with a poor prognosis. Emerging evidence has revealed that targeting senescent cells may be a potential treatment for IPF. In this study, we aimed to explore whether roxithromycin (RXM) can improve lung fibrosis by targeting senescent cells. First, we confirmed the ability of RXM to selectively kill senescent cells by inducing apoptosis and inhibiting the expression of senescence-associated secretory phenotype (SASP) factors, suggesting the potential role of RXM as a "senolytic" and "senomorphic" drug. Next, we observed that TGF-beta- and senescent cell-induced lung fibroblast activation was inhibited by RXM treatment, which prompted us to further investigate its effect in vivo. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, RXM was shown to attenuate lung injury, inflammation, and fibrosis. Furthermore, the senescent phenotype of lung tissues induced by BLM was significantly diminished after RXM administration, indicating the potential of RXM as an antifibrotic and antisenescent agent. Interestingly, NADPH oxidase 4 (NOX4), implicated in lung fibrosis and cell senescence, was shown to be inhibited by RXM treatments. The antifibroblast activation and antisenescent effects of RXM were abolished in NOX4 knockdown cells, demonstrating that RXM may ameliorate BLM-induced pulmonary fibrosis by targeting senescent cells mediated by the NOX4 pathway. Collectively, these data demonstrated that RXM may be a potential clinical agent for IPF and further supported the notion that targeting cellular senescence is a promising treatment for progressive age-related disease.
资助项目National Science and Technology Major Project Key New Drug Creation and Manufacturing Program[2019ZX09201001-004-010] ; National Science and Technology Major Project Key New Drug Creation and Manufacturing Program[2019ZX09201001-003-010] ; National Natural Science Foundation of China[U1703235] ; National Natural Science Foundation of China[31871414] ; National Science Fund for Distinguished Young Scholars[81125023] ; K. C. Wong Education Foundation
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000624397300003
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/295497]  
专题新药研究国家重点实验室
通讯作者Li, Jia; Zang, Yi
作者单位1.Pilot Natl Lab Marine Sci & Technol Qingdao, Open Studio Druggabil Res Marine Nat Prod, Qingdao 266237, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 200000, Peoples R China
5.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Xuan,Dong, Ying,Li, Wan-chen,et al. Roxithromycin attenuates bleomycin-induced pulmonary fibrosis by targeting senescent cells[J]. ACTA PHARMACOLOGICA SINICA,2021:11.
APA Zhang, Xuan,Dong, Ying,Li, Wan-chen,Tang, Bi-xi,Li, Jia,&Zang, Yi.(2021).Roxithromycin attenuates bleomycin-induced pulmonary fibrosis by targeting senescent cells.ACTA PHARMACOLOGICA SINICA,11.
MLA Zhang, Xuan,et al."Roxithromycin attenuates bleomycin-induced pulmonary fibrosis by targeting senescent cells".ACTA PHARMACOLOGICA SINICA (2021):11.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。