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Abstract: SA-PO573

MiRNA-424 in Exosomes from Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells Through p38 Activation

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Kwon, Soon hyo, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Republic of Korea, Seoul, Korea (the Republic of)
  • Kim, Hyoshik, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Republic of Korea, Seoul, Korea (the Republic of)
  • Noh, Hyunjin, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Republic of Korea, Seoul, Korea (the Republic of)
  • Kim, Yon hee, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Republic of Korea, Seoul, Korea (the Republic of)
  • Yu, Byung chul, Soonchunhyang University Bucheon Hospital, Republic of Korea, Bucheon, Korea (the Republic of)
Background

Tubular injury and fibrosis is associated with progressive kidney function decline in advanced glomerular disease. Glomerulo-tubular crosstalk is believed to contribute to tubular injury. Exosomal micro RNAs (miRNAs) are capable of modulation of distant cells. We hypothesized the exosomal miRNAs derived from injured podocyte lead to tubular epithelial cell damage.

Methods

As proof of concept, tubular epithelial cells (HK2 cell) were cultured with exosomes from puromycin-treated human podocytes or healthy podocytes. Damage to the HK2 cells was assessed. Through sequencing we identified the miRNA repertoire from podocyte exosomes. To validate the effect of the miRNAs, HK2 cells were treated with miRNA mimics.

Results

Exosomes from injured podocytes induced apoptosis and p38 phosphorylation of HK2 cells. RNAseq identified up-regulated 63 miRNAs in the exosomes from puromycin treated podocytes. Among them, 5 miRNAs (miR-149, 424, 542, 582 and 874) were selected as candidate miRNAs for tubular apoptosis according to a literature-based search. miRNA-424 mimics led to apoptosis of HK2 cells.

Conclusion

Exosomes from injured podocytes lead to damage in tubular epithelial cells. This may contribute to the development of tubular injury in glomerular disease.