Associations of urinary polymeric immunoglobulin receptor peptides in the context of cardio-renal syndrome

He, T., Siwy, J., Metzger, J., Mullen, W. , Mischak, H., Schanstra, J. P., Zürbig, P. and Jankowski, V. (2020) Associations of urinary polymeric immunoglobulin receptor peptides in the context of cardio-renal syndrome. Scientific Reports, 10, 8291. (doi: 10.1038/s41598-020-65154-2) (PMID:32427855) (PMCID:PMC7237418)

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Abstract

The polymeric immunoglobulin receptor (pIgR) transports immunoglobulins from the basolateral to the apical surface of epithelial cells. PIgR was recently shown to be associated with kidney dysfunction. The immune defense is initiated at the apical surface of epithelial cells where the N-terminal domain of pIgR, termed secretory component (SC), is proteolytically cleaved and released either unbound (free SC) or bound to immunoglobulins. The aim of our study was to evaluate the association of pIgR peptides with the cardio-renal syndrome in a large cohort and to obtain information on how the SC is released. We investigated urinary peptides of 2964 individuals available in the Human Urine Proteome Database generated using capillary electrophoresis coupled to mass spectrometry. The mean amplitude of 23 different pIgR peptides correlated negatively with the estimated glomerular filtration rate (eGFR, rho = −0.309, p < 0.0001). Furthermore, pIgR peptides were significantly increased in cardiovascular disease (coronary artery disease and heart failure) after adjustment for eGFR. We further predicted potential proteases involved in urinary peptide generation using the Proteasix algorithm. Peptide cleavage site analysis suggested that several, and not one, proteases are involved in the generation of the SC. In this large cohort, we could demonstrate that pIgR is associated with the cardio-renal syndrome and provided a more detailed insight on how pIgR can be potentially cleaved to release the SC.

Item Type:Articles
Additional Information:This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant number 764474. Joost P. Schanstra was supported by the “Fondation pour la Recherche Médicale” (grant number DEQ20170336759).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mischak, Professor Harald and Mullen, Dr Bill
Authors: He, T., Siwy, J., Metzger, J., Mullen, W., Mischak, H., Schanstra, J. P., Zürbig, P., and Jankowski, V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Scientific Reports 10: 8291
Publisher Policy:Reproduced under a Creative Commons License

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