Department of Anorectal Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China.
Acta Biochim Pol. 2020 Apr 3;67(2):157-163. doi: 10.18388/abp.2020_5152.
Herein, we unfolded miR-98-5p mechanism in inflammatory bowel disease (IBD). IBD mouse model was established. The severity of colitis was assessed daily using the disease activity index (DAI). Murine peritoneal macrophages were stimulated by lipopolysaccharide (LPS). MiR-98-5p, tribbles homolog 1 (Trib1), M1 and M2 macrophage marker genes mRNA expression was analyzed. The relationship between miR-98-5p and Trib1 was explored using a luciferase reporter assay. The strategy of loss-of-function was used to explore the mechanism of miR-98-5p in macrophage polarization, inflammation and IBD. The results revealed that IBD mice had higher DAI index and miR-98-5p expression when compared to the Sham group. MiR-98-5p and Trib1 displayed a targeted regulation relationship. Knockdown of miR-98-5p transformed LPS-induced M1 macrophage polarization into M2 macrophage polarization and inhibited inflammation via up-regulating Trib1. However, shTrib1 reversed the effects. In vivo experiment, silencing of miR-98-5p, diminished the DAI and promoted M2 macrophage polarization. In conclusion, knockdown of miR-98-5p changed macrophage polarization to the M2 phenotype by increasing Trib1 expression, thereby alleviating IBD symptoms.
在这里，我们揭示了 miR-98-5p 在炎症性肠病（IBD）中的作用机制。我们建立了 IBD 小鼠模型。每天使用疾病活动指数（DAI）评估结肠炎的严重程度。用脂多糖（LPS）刺激小鼠腹腔巨噬细胞。分析了 miR-98-5p、Tribbles 同源物 1（Trib1）、M1 和 M2 巨噬细胞标记基因的 mRNA 表达。通过荧光素酶报告基因检测探索了 miR-98-5p 与 Trib1 之间的关系。采用基因敲除策略探讨了 miR-98-5p 在巨噬细胞极化、炎症和 IBD 中的作用机制。结果表明，与 Sham 组相比，IBD 小鼠的 DAI 指数和 miR-98-5p 表达更高。miR-98-5p 和 Trib1 之间存在靶向调节关系。敲低 miR-98-5p 将 LPS 诱导的 M1 巨噬细胞极化为 M2 巨噬细胞，并通过上调 Trib1 抑制炎症。然而，shTrib1 逆转了这种作用。在体内实验中，沉默 miR-98-5p 可降低 DAI 并促进 M2 巨噬细胞极化。总之，敲低 miR-98-5p 通过增加 Trib1 表达将巨噬细胞极化为 M2 表型，从而减轻 IBD 症状。
