The role and therapeutic potential of exosome-mediated microRNAs regulatory networks in diabetic kidney disease.

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.