The dual role of exosomes in renal fibrosis and their potential for clinical translational applications

Abstract

Abstract Renal fibrosis is the core pathological process in the progression of chronic kidney disease to its end stage. There is to date no novel therapeutic strategies that are both safe and efficient in reversing renal fibrosis in humans. Exosomes, as key mediators of intercellular communication, play significant regulatory roles in renal fibrosis. Translating mechanistic studies on exosome-mediated promotion or inhibition of renal fibrosis into clinically applicable anti-fibrotic strategies remains a challenging issue in this field. In this review, we systematically elucidate the distinct dual role of exosomes, highlighting how they function as either pro-fibrotic drivers or anti-fibrotic protectors depending on their cellular origin. In particular, we examine how renal tubular epithelial cell-derived exosomes promote renal fibrosis through multiple mechanisms by delivering specific cargoes—including miRNAs (e.g., miR-21, miR-19b-3p), mRNA (TGF-β1), and proteins (OPN, TNFAIP8)—via signaling pathways such as PTEN/Akt, NF-κB, and HIF-1α. Furthermore, we discuss exosome-based therapeutic strategies, focusing on the anti-fibrotic potential of mesenchymal stem cell-derived exosomes and targeted engineering strategies, such as drug loading and surface modification. Finally, we also summarize the value of urinary and blood exosomes as biomarkers in the diagnosis of renal fibrosis. In conclusion, by decoding the dual nature of exosomes, we offer a comprehensive framework to accelerate the clinical translation of these nanovesicles into precise diagnostics and targeted therapeutics.