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- Title
Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway.
- Authors
Feng, Yun; Wang, Linlin; Ma, Xiaoying; Yang, Xiaotong; Don, Ocholi; Chen, Xiaoyan; Qu, Jieming; Song, Yuanlin
- 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.
- Subjects
GLUCAGON-like peptide 1; ADULT respiratory distress syndrome; CHORIONIC villi; NEUTROPHILS; TREATMENT effectiveness; WESTERN immunoblotting; LIRAGLUTIDE; LUNG injuries; MESENCHYMAL stem cells
- Publication
Stem Cell Research & Therapy, 2020, Vol 11, Issue 1, p1
- ISSN
1757-6512
- Publication type
Article
- DOI
10.1186/s13287-019-1492-6