文献类型：期刊文献

英文题名：RETRACTED: Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway (Retracted article. See vol. 14, 2023)

作者：Feng, Yun[1,2,3];Wang, Linlin[1,4];Ma, Xiaoying[5,6];Yang, Xiaotong[5,6];Don, Ocholi[2];Chen, Xiaoyan[7];Qu, Jieming[2,3];Song, Yuanlin[1,4,8,9]

机构：[1]Fudan Univ, Zhongshan Hosp, Dept Pulm Med, Shanghai 20003, Peoples R China;[2]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Respirat, Shanghai 20025, Peoples R China;[3]Shanghai Jiao Tong Univ, Inst Resp Dis, Sch Med, Shanghai 20025, Peoples R China;[4]Shanghai Resp Res Inst, Shanghai 20003, Peoples R China;[5]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[6]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[7]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Pathol, Shanghai 20025, Peoples R China;[8]Fudan Univ, Zhongshan Hosp, Qingpu Branch, Dept Pulm Med, Shanghai 201700, Peoples R China;[9]Fudan Univ, Huashan Hosp, Natl Clin Res Ctr Aging & Med, Shanghai 200040, Peoples R China

年份：2020

卷号：11

期号：1

外文期刊名：STEM CELL RESEARCH & THERAPY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000513179500002)】；

基金：This study was supported by the National Natural Science Foundation of China (81770075, 81630001, 81490533, 81570028, 81770039), the State Key Basic Research Program (973) project (2015CB553404), National Science & Technology Major Project `Key New Drug Creation and Manufacturing Program', China (2018ZX09201002-006), Shanghai Top-Priority Clinical Key Disciplines Construction Project (Respiratory Medicine), Shanghai Jiao Tong University Medical Cross Project (YG2017MS64), Shanghai Natural Science Foundation (18ZR1424000), Shanghai Shenkang Hospital Development Center Clinical Science and Technology Innovation Project (SHDC12018102), and National Innovative Research Team of High-level Local Universities in Shanghai.

语种：英文

外文关键词：ALI; ARDS; Mesenchymal stem cells; Liraglutide; Combination therapy

摘要：BackgroundALI/ARDS is the major cause of acute respiratory failure in critically ill patients. As human chorionic villi-derived MSCs (hCMSCs) could attenuate ALI in the airway injury model, and liraglutide, glucagon-like peptide 1 (GLP-1) agonist, possesses anti-inflammatory and proliferation promotion functions, we proposed to probe the potential combinatory effect of hCMSCs and liraglutide on ALI.MethodsWe examined the time- and dose-dependent manner of GLP-1R, SPC, Ang-1, and FGF-10 with LPS via western blot and qRT-PCR. Western blot and chromatin immunoprecipitation assay detected the effects of liraglutide on GLP-1R, SPC, Ang-1, and FGF-10 through PKAc/beta -catenin pathway and cAMP pathway. In the ALI animal model, we detected the effects of MSC and liraglutide combination on ALI symptoms by H&E staining, western blot, ELISA assays, calculating wet-to-dry ratio of the lung tissue, and counting neutrophils, leukocytes, and macrophages in mouse bronchoalveolar lavage fluid (BALF).ResultsThe data demonstrated that LPS reduced hCMSC proliferation and GLP-1R, SPC, Ang-1, and FGF-10 levels in a dose- and time-dependent manner. Liraglutide significantly dampened the reduction of GLP-1R, SPC, Ang-1, and FGF-10 and reversed the effect of LPS on hCMSCs, which could be regulated by GLP-1R and its downstream cAMP/PKAc/beta -catenin-TCF4 signaling. Combination of hCMSCs with liraglutide showed more therapeutic efficacy than liraglutide alone in reducing LPS-induced ALI in the animal model.ConclusionsThese results reveal that the combination of hCMSCs and liraglutide might be an effective strategy for ALI treatment.