S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung
作者机构:State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesInstitute of Materia MedicaChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100050China Department of OtolaryngologyHead and Neck SurgeryChildren's Hospital Capital Institute of PediatricsBeijing 100020China Department of Thoracic SurgeryPeking Union Medical College HospitalPeking Union Medical CollegeDong Cheng DistrictBeijing 100730China State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of PharmacologySchool of PharmaceuticalGuangzhou University of Chinese MedicineGuangzhou 510000China State Key Laboratory of Quality Research in Chinese MedicineMacao Institute for Applied Research in Medicine and HealthMacao University of Science and TechnologyTaipaMacao SAR 999078China
出 版 物:《Acta Pharmaceutica Sinica B》 (药学学报(英文版))
年 卷 期:2023年第13卷第3期
页 面:1110-1127页
核心收录:
学科分类:1002[医学-临床医学] 100201[医学-内科学(含:心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
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)
主 题:Idiopathic pulmonary fibrosis Endothelial barrier Tight junction Sphingosine-1-phosphate receptor 1 Sphingosine-1-phosphate receptor 1 agonist FTY720 IMMH002 Protein stability
摘 要:Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment *** median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung *** important components of lung tissue,endothelial cells(ECs)are associated with pulmonary ***,the role of endothelial dysfunction in pulmonary fibrosis(PF)is incompletely ***-1-phosphate receptor 1(S1PR1)is a G protein-coupled receptor highly expressed in lung *** expression is markedly reduced in patients with ***,we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin(BLM)*** 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 *** results suggest that S1PR1 might be a promising drug target for IPF therapy.