NDT Receptor Paper R2 clean.pdf (289.6 kB)
Download file

Reduced proximal tubular expression of protein endocytic receptors in proteinuria is associated with urinary receptor shedding.

Download (289.6 kB)
journal contribution
posted on 04.01.2018, 11:16 by Hiwa Fatah, Nura Benfaed, Ravinder S. Chana, Mohamed H. Chunara, Jonathan Barratt, Richard J. Baines, Nigel J. Brunskill
Background: Filtered proteins, including albumin, are reabsorbed in the proximal tubule (PT) mediated by megalin, cubilin and the neonatal Fc receptor (FcRn). Proteinuria is an important renal biomarker linked to poor prognosis but expression of these key receptors is not well studied. Methods: Megalin expression was determined at protein and messenger RNA (mRNA) levels in kidneys from proteinuric patients, and the expression of megalin, cubilin and FcRn was examined in the kidneys of mice with protein-overload proteinuria. The presence of receptors in the urine of proteinuric and control mice was also studied. Results: In nephrotic patients, megalin expression is reduced while mRNA is increased. In proteinuric mice megalin, cubilin and the neonatal FcRn protein are all reduced in PTs. Megalin and FcRn mRNA are increased in proteinuric mice, whereas that for cubilin was reduced. In proteinuric mice increased urinary excretion of each of these endocytic receptors was observed. Conclusions: It is concluded that in proteinuria, expression of all the key protein re-absorptive receptors is significantly reduced in the PT in association with increased turnover and urinary shedding.

Funding

M.H.C. reports grants from British Division of the International Academy of Pathology (BDIAP), and from International Academy of Pathology, during the conduct of the study.

History

Citation

Nephrology Dialysis Transplantation, 2017, gfx321

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

AM (Accepted Manuscript)

Published in

Nephrology Dialysis Transplantation

Publisher

Oxford University Press (OUP) for European Renal Association - European Dialysis and Transplant Association (ERA-EDTA)

issn

0931-0509

eissn

1460-2385

Acceptance date

01/10/2017

Copyright date

2017

Available date

23/11/2018

Publisher version

https://academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfx321/4656152

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en

Usage metrics

Categories

Exports