Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway
| العنوان: | Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway |
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| المؤلفون: | Xiaoyan Chen, Linlin Wang, Yun Feng, Xiaoying Ma, Ocholi Don, Yuanlin Song, Jieming Qu, Xiaotong Yang |
| المصدر: | Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-12 (2020) Stem Cell Research & Therapy |
| بيانات النشر: | BMC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Agonist, Lipopolysaccharides, Male, Combination therapy, medicine.drug_class, Acute Lung Injury, Medicine (miscellaneous), Pharmacology, Mesenchymal Stem Cell Transplantation, Transfection, Biochemistry, Genetics and Molecular Biology (miscellaneous), Glucagon-Like Peptide-1 Receptor, lcsh:Biochemistry, Mice, Western blot, Glucagon-Like Peptide 1, medicine, Cyclic AMP, Animals, Humans, Hypoglycemic Agents, lcsh:QD415-436, beta Catenin, lcsh:R5-920, medicine.diagnostic_test, Liraglutide, business.industry, Research, Cell Biology, respiratory system, Cyclic AMP-Dependent Protein Kinases, respiratory tract diseases, Mice, Inbred C57BL, ALI, Bronchoalveolar lavage, Molecular Medicine, cAMP-dependent pathway, Mesenchymal stem cells, ARDS, Stem cell, Chorionic Villi, business, lcsh:Medicine (General), Chromatin immunoprecipitation, Fibroblast Growth Factor 10, medicine.drug, Signal Transduction |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1757-6512 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a47b17ae7d878d9197027747a0468eaTest https://doaj.org/article/78ea6372573f44dbbac49f83cfbfbfafTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7a47b17ae7d878d9197027747a0468ea |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17576512 |
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