ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: FR-PO1050

Cellular Prion Protein Attenuates Renal Fibrosis by Interaction with Epithelial Growth Factor Receptor

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms


  • Song, Nana, Zhongshan Hospital Fudan University Department of Nephrology, Shanghai, China

Cellular prion protein (Prpc) coded by the Prnp gene, is a kind of cell-surface copper-binding protein, anchoring on cell membrane lipid rafts through glycosyl phosphatidyl inositol anchor (GPI), and plays an important role in cell information transmission. Prpc is expressed in the kidney. However, the role of Prpc in regulating fibrotic maladaptive repair of the injured kidney remains largely unknown.


Wild-type FVB mice, Prnp-/- mice were used for in vivo studies. Renal I/R injury model was induced by bilateral renal pedicle clamping for 35 minutes. Renal fibrosis models were induced by unilateral renal pedicle clamping for 30 minutes (UIR) and by unilateral ureteral obstruction (UUO). HK-2 cells were used for in vitro studies. HK-2 cells were treated with TGF-β induce EMT.


Prpc is overexpressed in the kidney biopsies from patients with CKD. This is supported by our experimental data showing that Prpc is gradually upregulated in the kidney following I/R, UIR and UUO insult and Prpc deletion by knocking out Prnp promoted AKI and facilitated fibrosis at later stages. Proteomics analysis indicated that the expression of key protein in DDR, including replication protein A (RPA), minichromosome maintenance protein 2/4/6 (MCM2/4/6) and cyclin-dependent kinases 1/2 (CDK1/2), as well as epidermal growth factor receptor (EGFR) drastically upregulate in the I/R kidney, while in Prnp-/- mice, EGFR rises even further with DDR-associated protein slumping. Furthermore, we uncover a critical role of Prpc in the control of EGFR signaling by promoting internalization of EGFR in renal tubular epithelia cells, which in turn influences DNA replication followed injury and renal fibrosis.


In summary, our study provides experimental evidence showing that Prpc plays an adaptive nephroprotective role by modulating activation of EGFR pathway and promoting cell cycle progression.


  • Government Support – Non-U.S.