载 miR-20a-5p 的 PLGA 微球通过 STAT3 介导的抑制 Th17 分化改善克罗恩病患者的肠道上皮屏障功能。

PLGA microspheres carrying miR-20a-5p improved intestinal epithelial barrier function in patients with Crohn's disease through STAT3-mediated inhibition of Th17 differentiation.

机构信息

Department of General Surgery, Taizhou People's Hospital Affiliated to Nanjing Medical University, No. 366 Taihu Road, Taizhou 225300, Jiangsu Province, China; Department of Anesthesiology, Taizhou People's Hospital Affiliated to Nanjing Medical University, No. 366 Taihu Road, Taizhou 225300, Jiangsu Province, China.

Department of Anesthesiology, Taizhou People's Hospital Affiliated to Nanjing Medical University, No. 366 Taihu Road, Taizhou 225300, Jiangsu Province, China.

出版信息

Int Immunopharmacol. 2022 Sep;110:109025. doi: 10.1016/j.intimp.2022.109025. Epub 2022 Jul 16.

DOI:10.1016/j.intimp.2022.109025

PMID:35853280

Abstract

BACKGROUND

Recent studies have shown that microRNAs (miRNAs) are aberrantly expressed in patients with Crohn's disease (CD). This suggests that the aberrant expression of miRNAs may contribute to the development of CD. Currently, the specific miRNAs involved in CD development have not been clearly identified. Therefore, we aimed to identify CD-associated miRNAs and explore their functions.

METHODS

miRNA microarray analysis was performed to screen for differentially expressed miRNAs in colon tissues from normal controls (NC) and CD patients. The identified miRNAs were validated using quantitative real-time PCR (qPCR). The therapeutic roles of miR-20a-5p mimics via the delivery of poly(lactic-co-glycolic acid) microspheres (PLGA MSs) were further investigated in IL-10 mice with spontaneous chronic colitis that were used as a model of CD. The target genes of miR-20a-5p and the associated signaling pathways were identified through bioinformatic analysis and experimental verification of the interactions between the targets predicted by the algorithms and dysregulated mRNAs.

RESULTS

The analysis showed that miR-20a-5p was the most significantly downregulated miRNA in patients with CD. Treatment with PLGA MSs carrying miR-20a-5p significantly ameliorated the colitis, decreased mucosal inflammation, and improved epithelial barrier function. Bioinformatic analysis and experimental studies showed that miR-20a-5p inhibition enhanced Th17 differentiation and improved intestinal epithelial barrier function by targeting STAT3.

CONCLUSIONS

Downregulation of miR-20a-5p improved the intestinal epithelial barrier function and prevented CD development through the STAT3/IL-17 signaling pathway. Therefore, the delivery of miR-20a-5p by PLGA MSs may serve as a potential therapeutic strategy for CD treatment.

摘要

背景

最近的研究表明，微小 RNA（miRNA）在克罗恩病（CD）患者中表达异常。这表明 miRNA 的异常表达可能有助于 CD 的发展。目前，与 CD 发展相关的特定 miRNA 尚未明确确定。因此，我们旨在鉴定与 CD 相关的 miRNA 并探索其功能。

方法

通过 miRNA 微阵列分析筛选正常对照（NC）和 CD 患者结肠组织中差异表达的 miRNA。使用定量实时 PCR（qPCR）验证鉴定的 miRNA。通过聚（乳酸-共-乙醇酸）微球（PLGA MS）递送 miR-20a-5p 模拟物进一步研究其在具有自发性慢性结肠炎的 IL-10 小鼠中的治疗作用，该模型用于模拟 CD。通过生物信息学分析和算法预测的靶基因与失调 mRNA 之间相互作用的实验验证，确定了 miR-20a-5p 的靶基因及其相关信号通路。