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

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.

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PID https://www.doi.org/10.6084/m9.figshare.c.4805130
PID https://www.doi.org/10.6084/m9.figshare.c.4805130.v1
URL http://dx.doi.org/10.6084/m9.figshare.c.4805130.v1
URL http://dx.doi.org/10.6084/m9.figshare.c.4805130
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Author Feng, Yun
Author Linlin Wang
Author Xiaoying Ma
Author Xiaotong Yang
Author Ocholi Don
Author Xiaoyan Chen
Author Jieming Qu
Author Yuanlin Song
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Publication Date 2020-01-01
Publisher figshare
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keyword FOS: Chemical sciences
keyword FOS: Health sciences
keyword FOS: Biological sciences
keyword FOS: Clinical medicine
system:type other
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Source https://science-innovation-policy.openaire.eu/search/other?orpId=dedup_wf_001::f8edc9e5447dda50f2c177736e0942f7
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Last Updated 20 December 2020, 02:06 (CET)
Created 20 December 2020, 02:06 (CET)