Emerging Roles of Exosomal miRNAs in Mediation of Kidney Stone Pathogenesis
Visetonu Victoria Vitsu, Chumchamo T. Humtsoe, Ananya Bhattacharjee, Manodeep Chakraborty, Ravi Kumar RajanIntroduction/Objective:
Nephrolithiasis is a complex kidney disease characterized by the development of kidney stones. Evidence is emerging that exosomal microRNAs (miRNAs) play a role in these processes. The present review briefs the role of exosomal miRNAs in stone pathogenesis in the kidney and their possible diagnostic and therapeutic implications.
Methods:
A narrative review was performed on exosomal miRNAs involved in calcium oxalate crystal formation and calcium and oxalate metabolism, oxidative stress, inflammation, renal injury, renal fibrosis, and immune responses in nephrolithiasis.
Results:
Multiple miRNA molecules were found to be linked to various components of stone formation and renal damage that were present in the exosomes. Monkeys with hypercalciuria and calcium oxalate stone formation showed an association with miR-148b-5p, and monkeys with inflammatory and cellular stress responses showed an association with miR-223-3p and miR-93-3p. A role for miR-21 and miR-214 in renal fibrosis and tissue injury was suggested. In contrast, miR-20b-3p, miR-186-5p and miR-374a-5p had the potential to exert protective actions by regulating inflammatory and injury-related pathways.
Discussion:
The role of exosomal miRNAs in nephrolithiasis could be involved in several path-ways and may be used as non-invasive, stable biomarkers. However, the challenges of exosome isolation and miRNA detection methods, experimental models, and limited clinical validation studies remain a great hurdle.
Conclusion:
Exosomal miRNAs are promising molecular regulators and potential biomarkers in nephrolithiasis. The diagnostic and therapeutic value of these must be further investigated through mechanistic and clinical studies.