Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway (Retracted article. See vol. 14, 2023)
Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway (Retracted article. See vol. 14, 2023)
复制标题
hCMSCs 和利拉鲁肽组合通过 cAMP/PKAc/β-catenin 信号通路对 ALI 的影响
DOI：
10.1186/s13287-019-1492-6
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发表时间：
2020-01-03
影响因子：
7.5
通讯作者：
Song, Yuanlin
中科院分区：
文献类型：
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作者：
Feng, Yun;Wang, Linlin;Song, Yuanlin
研究背景急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）是危重病人急性呼吸衰竭的主要原因。由于人绒毛膜绒毛来源的间充质干细胞（human chorionic villi-derived MSCs，hCMSCs）可以减轻气道损伤模型中的ALI，而利拉鲁肽（lir），胰高血糖素样肽1（glucagon-like peptide 1，GLP-1）激动剂，具有抗炎和促增殖的作用，我们提出探讨hCMSCs和利拉鲁肽联合治疗ALI的潜在作用。和FGF-10与LPS通过蛋白质印迹和qRT-PCR。Western blot和染色质免疫沉淀试验检测了利拉鲁肽通过PKAc/β-catenin途径和cAMP途径对GLP-1 R、SPC、Ang-1和FGF-10的影响。在ALI动物模型中，我们通过H&E染色、western blot、ELISA测定、计算肺组织的湿干比以及计数小鼠支气管肺泡灌洗液（BALF）中的中性粒细胞、白细胞和巨噬细胞来检测MSC和利拉鲁肽组合对ALI症状的影响。和FGF-10水平呈剂量和时间依赖性。利拉鲁肽可显著抑制GLP-1 R、SPC、Ang-1和FGF-10的降低，逆转LPS对hCMSC的作用，这可能通过GLP-1 R及其下游cAMP/PKAc/β-catenin-TCF 4信号转导途径进行调节。hCMSCs与利拉鲁肽联合应用在减轻LPS诱导的ALI方面比单独应用利拉鲁肽有更好的疗效。
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/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).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/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.ConclusionsThese results reveal that the combination of hCMSCs and liraglutide might be an effective strategy for ALI treatment.