Abstract: TH-PO1086

Differential Expression of miRNAs from Urinary Extracellular Vesicles Identify Pathogenesis of Kidney Stones and Randall’s Plaque in Humans

Session Information

Category: Mineral Disease

  • 1204 Mineral Disease: Nephrolithiasis

Authors

  • Sutthimethakorn, Suchitra, Mayo Clinic , Rochester, Minnesota, United States
  • Wang, Xiangling, Mayo Clinic, Rochester, Minnesota, United States
  • Chirackal, Robin Sunny, Mayo Clinic , Rochester, Minnesota, United States
  • Enders, Felicity T., Mayo Clinic, Rochester, Minnesota, United States
  • Rule, Andrew D., Mayo Clinic, Rochester, Minnesota, United States
  • Chanana, Pritha, Mayo Clinic, Rochester, Minnesota, United States
  • Jayachandran, Muthuvel, Mayo Clinic, Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic, Rochester, Minnesota, United States
Background

Kidney stone disease is a complex disease associating with various types of kidney cells. Activation of the kidney cells could influence the sorting of specific cargo, especially miRNAs into urinary extracellular vesicles (EVs) as well as the release of these EVs into urine, linking the patho- and physiological process of the kidney. However, the roles of miRNAs within urinary EVs of kidney stone disease remain largely unknown. The current study thus aimed to extensively define the changes of miRNAs in urinary EVs between varying degrees of stone formers and controls.

Methods

Bio-banked cells-free urine samples from kidney stone formers with low plaque (LP, n=4; < 5% papillary surface area coverage) and high plaque (HP, n=4; > 5% papillary surface area coverage), first-time stone formers (SF, n=4), and non-stone forming controls (n=4) were used in this study. Urinary EVs-derived miRNAs were extracted and analyzed by XRNA Exosome RNA-Seq Library Kit. Differentially expressed miRNAs (p-value < 0.05) between first-time stone formers and controls, and between HP and LP stone formers were validated by RT-qPCR method and submitted to DIANA-miRPath Bioinformatics tool for biological pathway prediction.

Results

Exosome RNA-Seq analysis revealed a total of 17 and 10 differentially expressed miRNAs between SF and controls, and between LP and HP stone formers, respectively. Pathway analysis demonstrated the involvement of these altered miRNAs in various cellular processes and signaling pathways such as endocytosis, TGF-beta signaling pathway, MAPK signaling pathway and focal adhesion. Interestingly, several altered miRNAs have been related to numerous kidney-related diseases, including kidney fibrosis, chronic kidney disease, and acute kidney injury. Thus far, RT-qPCR data confirmed the increased expression level of hsa-miR-1299 in the SF group, as compared to the controls.

Conclusion

These findings revealed the changes in miRNAs profile within urinary EVs and their possible roles in kidney stone pathogenesis as well as the formation of Randall’s plaque. Further investigations of these potential miRNAs may lead to better understanding of pathogenic mechanism underlying calcium-based kidney stone disease.