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Kidney Week

Abstract: FR-PO981

Role of Kidney Derived Extracellular Vesicles Containing Mitochondrial Proteins and Splicing Factors in Renal Fibrosis

Session Information

  • CKD: Pathobiology - I
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Maremanda, Krishna Prahlad, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Roy Chowdhury, Chitran, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Ajay, Amrendra Kumar, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Sabbisetti, Venkata, Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

Extracellular vesicles (EVs) are lipid bilayer nanoparticles enriched with biomolecules such as DNAs, RNAs, protein and lipids. They help in cellular communication and have potential theranostic applications based on their nature and origin. Organ-specific EVs have been shown to play pathophysiological role including fibrosis.

Methods

Here we describe the role of kidney specific EVs in initiating and promoting kidney fibrosis in mouse models. Kidneys were isolated from three mechanistically different animal models of chronic kidney injury which includes mice treated with Folic acid (FA), aristolochic acid (AA), and unilateral ureteral obstruction (UUO).

Results

Kidney specific EVs were isolated by restricted enzymatic digestion followed by differential centrifugations. Isolated EVs were characterized using TEM and by western blotting for enrichment of different exosomal protein markers, including CD63, flotillin-1, and alix. Enriched EVs from kidneys isolated from untreated and FA-treated mice were used for differential gene expression and proteomic studies. Gene expression analysis showed that these EVs were enriched in various splicing factors, including SRp40 along with its interacting lncRNA partners such as NEAT1, which are shown to be upregulated in fibrotic conditions. We also found that EVs isolated from fibrotic kidneys are enriched with various pro-fibrotic signaling molecules including EDA+ Fn, Col1A1 and TGF-β1. Proteomic analysis showed several differentially expressed proteins in various EVs isolated from fibrotic kidneys.

Conclusion

We found novel targets for kidney fibrosis in EVs.

Funding

  • NIDDK Support