The cellular prion protein is a stress protein secreted by renal tubular cells and a urinary marker of kidney injury
Open Access
- 17 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (4), 1-16
- https://doi.org/10.1038/s41419-020-2430-3
Abstract
Endoplasmic Reticulum (ER) stress underlies the pathogenesis of numerous kidney diseases. A better care of patients with kidney disease involves the identification and validation of ER stress biomarkers in the early stages of kidney disease. For the first time to our knowledge, we demonstrate that the prion protein PrPC is secreted in a conventional manner by ER-stressed renal epithelial cell under the control of the transcription factor x-box binding protein 1 (XBP1) and can serve as a sensitive urinary biomarker for detecting tubular ER stress. Urinary PrPC elevation occurs in patients with chronic kidney disease. In addition, in patients undergoing cardiac surgery, detectable urine levels of PrPC significantly increase after cardiopulmonary bypass, a condition associated with activation of the IRE1-XBP1 pathway in the kidney. In conclusion, our study has identified PrPC as a novel urinary ER stress biomarker with potential utility in early diagnosis of ongoing acute or chronic kidney injury.Keywords
Funding Information
- Agence Nationale de la Recherche
This publication has 47 references indexed in Scilit:
- ER-stress-induced transcriptional regulation increases protein synthesis leading to cell deathNature, 2013
- Endoplasmic reticulum stress induces PRNP prion protein gene expression in breast cancerBreast Cancer Research, 2013
- Suppression of XBP1S Mediates High Glucose-Induced Oxidative Stress and Extracellular Matrix Synthesis in Renal Mesangial Cell and Kidney of Diabetic RatsPLOS ONE, 2013
- α-Secretase-Derived Cleavage of Cellular Prion Yields Biologically Active Catabolites with Distinct FunctionsNeurodegenerative Diseases, 2012
- Prion protein: From physiology to cancer biologyCancer Letters, 2010
- Diagnosis of Acute Kidney Injury: From Classic Parameters to New BiomarkersContributions to nephrology, 2007
- Rapamycin inhibits human renal epithelial cell proliferation: Effect on cyclin D3 mRNA expression and stabilityKidney International, 2005
- Quality control in the endoplasmic reticulumNature Reviews Molecular Cell Biology, 2003
- The Role of Disulfide Bridge in the Folding and Stability of the Recombinant Human Prion ProteinOnline Journal of Public Health Informatics, 2001
- Tunicamycin inhibition of polyisoprenyl N-acetylglucosaminyl pyrophosphate formation in calf-liver microsomesBiochemical and Biophysical Research Communications, 1975