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Abstract: FR-PO734

Exosomes Generated from Cystic Renal Epithelial Cells Regulate Cellular Communication and Cystogenesis in ADPKD

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Ding, Hao, Mayo Clinic, Rochester, Minnesota, United States
  • Li, Xiaoyan, Mayo Clinic, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Clinic, Rochester, Minnesota, United States
  • Li, Xiaogang, Mayo Clinic, Rochester, Minnesota, United States
Background

The exosomes have recently drawn considerable interest as they are implicated in many pathophysiological processes of human diseases, including ADPKD. Cells can use these vesicles to communicate with both adjacent cells via the molecules present on the surface of these vesicles and distant cells via the circulation. Urinary exosomes have been proposed as a potential diagnostic tool in ADPKD. However, the basic cell biological understanding of the exosomes in cellular communication and the role of circulating exosomes in ADPKD is lacking.

Methods

To investigate if exosomes regulate cell-to-cell communication and cystogenesis, we isolated exosomes from urine of ADPKD patients and normal individuals (control) as well as from culture media of Pkd1+/+ and null renal epithelial cells. The isolated exosomes were used to treat Pkd1+/+ renal epithelial cells for a cell proliferation assay and cystogenesis in 3D cultures. Circulating exosomes was isolated from blood to evaluate if exosomal PD-L1 is associated with disease progression of ADPKD and with response to treatment in PKD animals.

Results

We found that treatment with exosomes isolated from ADPKD patient urine and from media of cystic renal epithelial cells increased cell proliferation of NRK-52E cells and mIMCD cells compared to those cells treated with exosomes isolated from normal individuals and wild type renal cells in an exosome concentration dependent manner. In addition, we found that NRK-52E cells treated with ADPKD urinary exosomes developed cysts-like structures in collagen gels within 2 days, which continued to grow progressively up to day 8, whereas NRK-52E cells treated with normal urinary exosomes only developed tubule-like structures in collagen gel up to day 8. We further found that urinary ADPKD exosomes induced the activation of ERK and mTOR signaling in treated cells. The expression of PD-L1 was increased in cystic renal epithelial cells and we are now evaluating if the increase of PD-L1 in exosomes isolated from bloods of PKD animals and ADPKD patients can be used as a biomarker for ADPKD.

Conclusion

Urinary ADPKD exosomes and exosomes from cystic renal epithelial cells regulate renal epithelial cells proliferation and cystogenesis. The levels of PD-L1 in circulating exosomes may be a potential biomarker for ADPKD.

Funding

  • NIDDK Support