2. Academic Validation
  3. Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway

Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway

  • Stem Cell Res Ther. 2020 Jan 3;11(1):2. doi: 10.1186/s13287-019-1492-6.
Yun Feng 1 2 3,  Linlin Wang 1 4,  Xiaoying Ma 5,  Xiaotong Yang 5,  Ocholi Don 2,  Xiaoyan Chen 6,  Jieming Qu 7 8,  Yuanlin Song 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 20003, China.
  • 2 Department of Respiration, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 20025, China.
  • 3 Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 20025, China.
  • 4 Shanghai Respiratory Research Institute, Shanghai, 20003, China.
  • 5 State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.
  • 6 Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 20025, China.
  • 7 Department of Respiration, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 20025, China. jmqu0906@163.com.
  • 8 Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 20025, China. jmqu0906@163.com.
  • 9 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 20003, China. ylsong70@163.com.
  • 10 Shanghai Respiratory Research Institute, Shanghai, 20003, China. ylsong70@163.com.
  • 11 Department of Pulmonary Medicine, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, 201700, China. ylsong70@163.com.
  • 12 National Clinical Research Center for Aging & Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China. ylsong70@163.com.
PMID: 31900217 DOI: 10.1186/s13287-019-1492-6
Abstract

Background: ALI/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.

Methods: We 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/β-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).

Results: The 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/β-catenin-TCF4 signaling. Combination of hCMSCs with liraglutide showed more therapeutic efficacy than liraglutide alone in reducing LPS-induced ALI in the animal model.

Conclusions: These results reveal that the combination of hCMSCs and liraglutide might be an effective strategy for ALI treatment.

Keywords

ALI; ARDS; Combination therapy; Liraglutide; Mesenchymal stem cells.

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