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微小RNA作为肠道屏障功能的关键调节因子:模式识别受体、上皮连接复合体及治疗方法

MicroRNAs as Key Modulators of Intestinal Barrier Function: Pattern Recognition Receptors, Epithelial Junctional Complexes, and Therapeutic Approaches.

作者信息

Sevim Rezzan, Erhan Songül, Matur Erdal

机构信息

Institute of Graduate Studies, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Department of Physiology, Faculty of Veterinary Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

出版信息

Dig Dis Sci. 2025 Jun 21. doi: 10.1007/s10620-025-09131-7.

DOI:10.1007/s10620-025-09131-7
PMID:40544176
Abstract

PURPOSE

This review aims to investigate the regulatory role of microRNAs (miRNAs) in intestinal barrier function, with a focus on their interaction with pattern recognition receptors (PRRs) such as Toll-like receptors (TLR2, TLR4, TLR5) and nucleotide-binding oligomerization domain (NOD) receptors. Additionally, the review explores how miRNAs influence epithelial junctional complexes-including tight junctions, adherens junctions, and desmosomes-and their implications in inflammatory bowel diseases (IBD).

METHODS

A comprehensive literature review was conducted to examine recent studies focusing on miRNA-mediated modulation of signaling pathways related to PRRs and junctional complexes. Particular attention was given to the expression and regulation of key junctional complexes such as claudin, occludin, and zonula occludens, and their relationship with epithelial homeostasis.

RESULTS

Emerging evidence demonstrates that miRNAs modulate both inflammatory signaling and structural junctional integrity. Dysregulated expression of specific miRNAs is associated with impaired barrier function and increased intestinal permeability, contributing to the pathogenesis of IBD. Moreover, experimental data suggest that miRNA mimics and antagomiRs may help restore epithelial barrier integrity and reduce inflammation.

CONCLUSION

MiRNAs play a central role in maintaining intestinal barrier homeostasis by targeting PRRs and junctional complexes. Their ability to modulate inflammation and barrier function highlights their potential as therapeutic targets. miRNA-based strategies may offer novel, targeted treatments for IBD and other intestinal disorders.

摘要

目的

本综述旨在研究微小RNA(miRNA)在肠道屏障功能中的调节作用,重点关注其与模式识别受体(PRR)如Toll样受体(TLR2、TLR4、TLR5)和核苷酸结合寡聚化结构域(NOD)受体的相互作用。此外,本综述还探讨了miRNA如何影响上皮连接复合体,包括紧密连接、黏着连接和桥粒,以及它们在炎症性肠病(IBD)中的意义。

方法

进行了全面的文献综述,以研究最近关注miRNA介导的与PRR和连接复合体相关信号通路调节的研究。特别关注关键连接复合体如闭合蛋白、闭锁蛋白和紧密连接带的表达和调节,以及它们与上皮稳态的关系。

结果

新出现的证据表明,miRNA可调节炎症信号和结构连接完整性。特定miRNA的表达失调与屏障功能受损和肠道通透性增加有关,这有助于IBD的发病机制。此外,实验数据表明,miRNA模拟物和抗miR可能有助于恢复上皮屏障完整性并减轻炎症。

结论

miRNA通过靶向PRR和连接复合体在维持肠道屏障稳态中发挥核心作用。它们调节炎症和屏障功能的能力突出了其作为治疗靶点的潜力。基于miRNA的策略可能为IBD和其他肠道疾病提供新的靶向治疗方法。

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