Adipose-derived mesenchymal stem cells (ADMSCs) have been used for treating tissue injury, and preactivation enhances their therapeutic effect. This study is aimed at investigating the therapeutic effect of activated ADMSCs by IL-1β on the intestinal ischaemia-reperfusion (IR) injury and exploring potential mechanisms. ADMSCs were pretreated with IL-1β in vitro, and activation of ADMSCs was assessed by α-SMA and COX-2 expressions and secretary function. Activated ADMSCs was transplanted into IR-injured intestine in a mouse model, and therapeutic effect was evaluated. In addition, to explore underlying mechanisms, COX-2 expression was silenced to investigate its role in activated ADMSCs for treatment of intestinal IR injury. When ADMSCs were pretreated with 50 ng/ml IL-1β for 24 hr, expressions of α-SMA and COX-2 were significantly upregulated, and secretions of PGE₂, SDF-1, and VEGF were increased. When COX-2 was silenced, the effect of IL-1β treatment was abolished. Activated ADMSCs with IL-1β significantly suppressed inflammation and apoptosis and enhanced healing of intestinal IR injury in mice, and these effects were impaired by COX-2 silencing. The results of RNA sequencing suggested that compared with the IR injury group activated ADMSCs induced alterations in mRNA expression and suppressed the activation of the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways induced by intestinal IR injury, whereas silencing COX-2 impaired the suppressive effect of activated ADMSCs on these pathway activations induced by IR injury. These data suggested that IL-1β pretreatment enhanced the therapeutic effect of ADMSCs on intestinal IR injury repairing via activating ADMSC COX-2-PGE₂ signaling axis and via suppressing the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways in the intestinal IR-injured tissue.

中文翻译：

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IL-1β激活的脂肪来源的MSC（ADMSC）对通过COX-2-PGE2信号修复肠缺血再灌注损伤的增强作用。

脂肪来源的间充质干细胞（ADMSC）已用于治疗组织损伤，预激活可增强其治疗效果。此研究的目的是调查通过IL-1活化的ADMSCs的治疗效果β对肠缺血再灌注（IR）损伤和探索的潜在机制。的ADMSCs用IL-1预处理β在体外，和的ADMSCs的活化是通过评估α-SMA和COX-2表达式以及秘书功能。将活化的ADMSCs移植到小鼠模型的IR损伤的肠中，并评估治疗效果。此外，为探讨潜在的机制，沉默了COX-2的表达以研究其在活化的ADMSC中治疗肠道IR损伤的作用。当的ADMSCs分别用50ng / ml的IL-1预处理β 24小时，表达α -SMA和COX-2的上调显著，和PGE的分泌物₂，SDF-1，和VEGF均升高。当COX-2沉默时，IL- 1β治疗的作用消失。活化的ADMSCs与IL-1 β可显着抑制小鼠的炎症和细胞凋亡，并增强肠道IR损伤的愈合，而COX-2沉默可削弱这些作用。RNA测序的建议，与IR损伤组激活的ADMSCs相比诱导mRNA表达的改变和抑制NF-的激活结果κ B-P65，MAPK-ERK1 / 2，并通过肠IR损伤诱导PI3K-AKT途径，而沉默COX-2会削弱激活的ADMSC对IR损伤诱导的这些途径激活的抑制作用。这些数据表明，IL-1 β预处理增强对肠道IR损伤的ADMSCs通过激活ADMSC COX-2-PGE修复的治疗效果_2个信令轴和经由抑制NF- κ肠道IR损伤的组织中的B-P65，MAPK-ERK1 / 2和PI3K-AKT途径。