S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung  

作　　者：Mengyao Hao Rong Fu Jun Tai Zhenhuan Tian Xia Yuan Yang Chen Mingjin Wang Huimin Jiang Ming Ji Fangfang Lai Nina Xue Liping Bai Yizhun Zhu Xiaoxi Lv Xiaoguang Chen Jing Jin 

机构地区：[1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100050,China [2]Department of Otolaryngology,Head and Neck Surgery,Children's Hospital Capital Institute of Pediatrics,Beijing 100020,China [3]Department of Thoracic Surgery,Peking Union Medical College Hospital,Peking Union Medical College,Dong Cheng District,Beijing 100730,China [4]State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China [5]Department of Pharmacology,School of Pharmaceutical,Guangzhou University of Chinese Medicine,Guangzhou 510000,China [6]State Key Laboratory of Quality Research in Chinese Medicine,Macao Institute for Applied Research in Medicine and Health,Macao University of Science and Technology,Taipa,Macao SAR 999078,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第3期1110-1127,共18页药学学报（英文版）

基　　金：supported by National Key Research&Development Program from the Ministry of Science and Technology of the PRC(No.2019YFE0111800,China);National Natural Science Foundation of China(No.81872923,China);Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2021-JKCS-016,China);The Science and Technology Development Fund,Macao SAR(No.0074/2019/AMJ,China).

摘　　要：Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation.As important components of lung tissue,endothelial cells(ECs)are associated with pulmonary diseases.However,the role of endothelial dysfunction in pulmonary fibrosis(PF)is incompletely understood.Sphingosine-1-phosphate receptor 1(S1PR1)is a G protein-coupled receptor highly expressed in lung ECs.Its expression is markedly reduced in patients with IPF.Herein,we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin(BLM)challenge.Selective activation of S1PR1 with an S1PR1 agonist,IMMH002,exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier.These results suggest that S1PR1 might be a promising drug target for IPF therapy.

关 键 词：Idiopathic pulmonary fibrosis Endothelial barrier Tight junction Sphingosine-1-phosphate receptor 1 Sphingosine-1-phosphate receptor 1 agonist FTY720 IMMH002 Protein stability 

分 类 号：R563[医药卫生—呼吸系统]