Zhang Xiaofei, Zhang Kexin, Fan Qiming, Sang Jiajun, Kan Chengxia, Pan Ruiyan, Sun Xiaodong, Hou Ningning, Guo Zhentao
Department of Endocrinology and Metabolism, Shandong Provincial Key Medical and Health Discipline of Endocrinology and Laboratory of Endocrinology and Metabolic Diseases, Clinical Research Center, Affiliated Hospital of Shandong, Second Medical University, Weifang, China.
Department of Nephrology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China.
Mol Biol Rep. 2025 Sep 13;52(1):902. doi: 10.1007/s11033-025-11015-y.
Diabetic kidney disease (DKD), a leading cause of end-stage renal disease, involves complex pathological mechanisms such as inflammation, fibrosis, oxidative stress, and immune dysregulation. Exosome-mediated microRNAs (miRNAs), as stable carriers of genetic material in body fluids, have emerged as crucial regulators of DKD progression by modulating intercellular communication and gene expression. This review summarizes the biogenesis and regulatory mechanisms of exosome-encapsulated miRNAs, highlighting their roles in glomerular injury, tubulointerstitial fibrosis, and immunoinflammatory responses in DKD. Specific exosomal miRNAs, including miR-21, miR-29, miR-192, and miR-155, are discussed for their contributions to renal cell injury and fibrotic progression. Moreover, exosomal miRNAs demonstrate significant potential as noninvasive biomarkers for early DKD diagnosis and disease monitoring, given their stability and tissue-specific expression profiles. Therapeutically, interventions targeting pathogenic miRNAs or delivering protective miRNAs via engineered exosomes offer promising strategies for DKD treatment. Despite current challenges related to standardization, delivery efficiency, and safety, advances in exosome engineering and nucleic acid therapeutics are expected to accelerate the clinical translation of exosomal miRNA-based precision medicine in DKD.
糖尿病肾病（DKD）是终末期肾病的主要原因，涉及炎症、纤维化、氧化应激和免疫失调等复杂的病理机制。外泌体介导的微小RNA（miRNA）作为体液中遗传物质的稳定载体，已成为通过调节细胞间通讯和基因表达来调控DKD进展的关键因子。本综述总结了外泌体包裹的miRNA的生物发生和调控机制，重点阐述了它们在DKD的肾小球损伤、肾小管间质纤维化和免疫炎症反应中的作用。讨论了特定的外泌体miRNA，包括miR-21、miR-29、miR-192和miR-155对肾细胞损伤和纤维化进展的作用。此外，鉴于外泌体miRNA的稳定性和组织特异性表达谱，它们作为DKD早期诊断和疾病监测的无创生物标志物具有巨大潜力。在治疗方面，针对致病miRNA或通过工程化外泌体递送保护性miRNA的干预措施为DKD治疗提供了有前景的策略。尽管目前在标准化、递送效率和安全性方面存在挑战，但外泌体工程和核酸治疗的进展有望加速基于外泌体miRNA的精准医学在DKD中的临床转化。
