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Neatl-miRNA204-5p-PI3K-AKT axis as a potential mechanism for photodynamic therapy treated colitis in mice

机译：Neatl-miRNA204-5p-PI3K-AKT轴作为光动力疗法治疗小鼠结肠炎的潜在机制

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Background: Inflammatory bowel disease (IBD) is a group of inflammatory conditions characterized by chronic inflammation of the gastrointestinal (GI) tract. Recent preclinical and clinical studies have shown the therapeutic value of photodynamic therapy with low doses of photosensitizer and/or light in colitis treatment, but the detailed mechanism is unclear.Methods: We examined 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy (PDT) in dextran sulfate sodium (DSS)-induced colitis in mice. Endoscopic and macroscopic observations as well as the Disease Activity Index score (DAI) was used to monitor the disease. Cytokine expression was measured by quantitative RT-PCR analysis to evaluate the efficacy of PDT. We applied the Clariom (TM) D bioinformatics analysis to investigate the differentially expressed genes after PDT. Finally, we used quantitative RT-PCR analysis and Western blotting to validate the targets of differentially expressed genes.Results: 5-ALA-PDT improved the DAI score and decreased the expression of various inflammatory cytokines. The Clariom (TM) D bioinformatics analysis identified 2043 diff ;erentially expressed genes (702 up-regulated and 1341 down-regulated). We confirmed the down-regulation of lncRNA-Neat1, lncRNA-Snhg5 and lncRNA-Gm9926 and the up-regulation of miRNA-204-5p, miRNA-218-5p, miRNA-200a-3p and miRNA-466h-5p. Additionally, the decreased expression level of the AKT3, p-AKT3, PI3K, p-PI3K protein were confirmed.Conclusions: This study provides in vivo comprehensive lncRNA and miRNA microarray analysis after 5-ALA-PDT treatment in DSS-induced colitis, and it may help to develop novel lncRNA-miRNA-related therapeutic approaches, such as the Neat1-miRNA204-5p-PI3K-AKT axis, to further increase the efficiency of PDT in IBD.
机译：背景：炎性肠病（IBD）是一组以胃肠道（GI）慢性炎症为特征的炎症性疾病。最近的临床前和临床研究表明，低剂量光敏剂和/或光对光动力疗法在结肠炎治疗中具有治疗价值，但具体机理尚不清楚。方法：我们检查了5-氨基乙酰丙酸（5-ALA）介导的光动力疗法（葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎中的PDT）。内窥镜和宏观观察以及疾病活动指数评分（DAI）用于监测疾病。通过定量RT-PCR分析测量细胞因子表达以评估PDT的功效。我们应用了Clariom（TM）D生物信息学分析来研究PDT后差异表达的基因。最后，我们使用定量RT-PCR分析和Western印迹法验证了差异表达基因的靶点。结果：5-ALA-PDT改善了DAI评分并降低了各种炎性细胞因子的表达。 Clariom（TM）D生物信息学分析鉴定了2043个差异表达基因（702个上调和1341个下调）。我们证实了lncRNA-Neat1，lncRNA-Snhg5和lncRNA-Gm9926的下调以及miRNA-204-5p，miRNA-218-5p，miRNA-200a-3p和miRNA-466h-5p的上调。此外，证实了AKT3，p-AKT3，PI3K，p-PI3K蛋白的表达水平降低。结论：本研究提供了5-ALA-PDT治疗DSS引起的结肠炎后体内的lncRNA和miRNA微阵列分析。它可能有助于开发与lncRNA-miRNA相关的新型治疗方法，例如Neat1-miRNA204-5p-PI3K-AKT轴，以进一步提高IBD中PDT的效率。

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