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Bone marrow mesenchymal stem cells protect alveolar macrophages from lipopolysaccharide-induced apoptosis partially by inhibiting the Wnt/beta-catenin pathway

机译:骨髓间充质干细胞通过抑制Wnt /β-catenin途径部分保护肺泡巨噬细胞免受脂多糖诱导的细胞凋亡

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Apoptosis of alveolar macrophages (AMs) plays a pathogenic role in acute lung injury (ALI) and its severe type, acute respiratory distress syndrome (ARDS). Mesenchymal stem cells (MSCs) are promising therapeutic cells for preventing apoptosis and eliminating cellular injury. We investigated the effects of rat bone marrow mesenchymal stem cells (BMSCs) on lipopolysaccharide (LPS)-induced apoptosis in AMs using transwell experiments, and examined the underlying mechanisms LPS induced AMs apoptosis in a dose- and time-dependent fashion, whereas BMSCs reduced AMs apoptosis when co-cultured at appropriate ratios. BMSCs decreased expression of cleaved caspase-3 and the pro-apoptotic protein, Bax, whilst increased levels of the anti-apoptotic protein, Bcl-2, prolonging the lifespan of AMs in vitro. Promotion of AMs survival by BMSCs required down-regulation of p-GSK-3 and -catenin in AMs. The anti-apoptosis action of BMSCs was reversed by SB216763, a specific inhibitor of GSK-3 that also activates Wnt/-catenin signaling. In conclusion, BMSCs can attenuate AM apoptosis partially by suppressing the Wnt/-catenin pathway.
机译:肺泡巨噬细胞(AMs)的凋亡在急性肺损伤(ALI)及其严重类型急性呼吸窘迫综合征(ARDS)中起致病作用。间充质干细胞(MSCs)是预防细胞凋亡和消除细胞损伤的有前途的治疗细胞。我们使用Transwell实验研究了大鼠骨髓间充质干细胞(BMSCs)对脂多糖(LPS)诱导的AMs凋亡的影响,并研究了LPS诱导AMs凋亡的潜在机制,呈剂量和时间依赖性,而BMSCs减少当以适当比例共培养时,AMs凋亡。 BMSCs减少了裂解的caspase-3和促凋亡蛋白Bax的表达,同时增加了抗凋亡蛋白Bcl-2的水平,从而延长了AMs的寿命。 BMSCs促进AMs存活需要下调AMs中的p-GSK-3和-catenin。 BMSCs的抗凋亡作用被SB216763逆转,SB216763是GSK-3的一种特异性抑制剂,也可以激活Wnt / -catenin信号传导。总之,骨髓间充质干细胞可以通过抑制Wnt / -catenin途径部分减弱AM凋亡。

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