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糖尿病肾病中非编码RNA调控网络与靶向治疗的研究进展

Research progress on non-coding RNA regulatory networks and targeted therapy in diabetic nephropathy.

作者信息

Wang Xiaxia, Jing Ruge, Yang Tong, Shao Ruiwen, Yang Fan, Shi Yangyang, Yang Xiujuan, An Dong, Liang Yonglin

机构信息

School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.

Teaching Experiment Training Center, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.

出版信息

Front Endocrinol (Lausanne). 2025 Jul 29;16:1625307. doi: 10.3389/fendo.2025.1625307. eCollection 2025.

DOI:10.3389/fendo.2025.1625307
PMID:40801037
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12339344/
Abstract

Diabetic Nephropathy (DN), a leading cause of disability and mortality in patients with diabetes, has become a complex global clinical issue that poses a severe challenge to public health. Research indicates that Non-coding RNAs (ncRNAs) participate in cell death and fibrosis through an endogenous competitive RNA (ceRNA) network. This network regulates kidney-specific cells such as podocytes, mesangial cells, and renal tubular epithelial cells, thereby establishing a multifaceted regulatory mechanism in DN progression. Furthermore, exosomal ncRNAs and their ceRNA networks, stem cell-derived exosomal ncRNAs, related biomolecules, and the targeted regulation of ncRNAs and ceRNA networks by traditional Chinese medicine all play significant roles in the advancement of DN. This review systematically summarizes the content of ncRNAs, ceRNA networks and DN, exosome ncRNA intervention in DN progression, and targeted regulation of ncRNA intervention in DN progression. Concurrently, it discusses the research progress and therapeutic status of ncRNAs as clinical biomarkers, challenges facing ncRNA-targeted therapy, therapeutic efficacy of exosomal ncRNAs and stem cell-derived exosomal ncRNAs, pharmacokinetic limitations of Chinese medicine components in regulating DN progression through ncRNA intervention, and analyses the bottlenecks in ncRNA-based diagnosis and cross-species conservation of circRNAs/lncRNAs. This study aimed to provide new insights for the in-depth exploration of the molecular mechanisms underlying DN and the development of targeted therapeutic strategies.

摘要

糖尿病肾病（DN）是糖尿病患者致残和致死的主要原因，已成为一个复杂的全球性临床问题，对公共卫生构成严峻挑战。研究表明，非编码RNA（ncRNAs）通过内源性竞争RNA（ceRNA）网络参与细胞死亡和纤维化过程。该网络调节足细胞、系膜细胞和肾小管上皮细胞等肾脏特异性细胞，从而在DN进展中建立多方面的调节机制。此外，外泌体ncRNAs及其ceRNA网络、干细胞衍生的外泌体ncRNAs、相关生物分子以及中药对ncRNAs和ceRNA网络的靶向调控在DN进展中均发挥重要作用。本综述系统总结了ncRNAs、ceRNA网络与DN的相关内容、外泌体ncRNA对DN进展的干预以及ncRNA干预DN进展的靶向调控。同时，讨论了ncRNAs作为临床生物标志物的研究进展和治疗现状、ncRNA靶向治疗面临的挑战、外泌体ncRNAs和干细胞衍生的外泌体ncRNAs的治疗效果、中药成分通过ncRNA干预调节DN进展的药代动力学局限性，并分析了基于ncRNA的诊断瓶颈以及环状RNA/长链非编码RNA的跨物种保守性。本研究旨在为深入探索DN的分子机制和开发靶向治疗策略提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d26/12339344/94e915e0fdb3/fendo-16-1625307-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d26/12339344/8ec6f7b7f069/fendo-16-1625307-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d26/12339344/94e915e0fdb3/fendo-16-1625307-g008.jpg
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本文引用的文献

1
Urinary exosomes exacerbate diabetic kidney disease by promoting NLRP3 inflammasome activation via the microRNA-516b-5p/SIRT3/AMPK pathway.尿液外泌体通过微小RNA-516b-5p/沉默调节蛋白3/腺苷酸活化蛋白激酶途径促进NLRP3炎性小体激活，从而加重糖尿病肾病。
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