Steroid regulation: an overlooked aspect of tolerance and chronic rejection in kidney transplantation

Christakoudi, S. et al. (2018) Steroid regulation: an overlooked aspect of tolerance and chronic rejection in kidney transplantation. Molecular and Cellular Endocrinology, 473, pp. 205-216. (doi:10.1016/j.mce.2018.01.021) (PMID:29427591)

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Abstract

Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n = 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation.

Item Type:Articles
Additional Information:The authors acknowledge financial support from FP7-HEALTH-2012-INNOVATION-1 (project number 305147: BIO-DrIM) and Medical Research Council MRC (grants G0801537/ID: 88245 and MRC Centre for Transplantation, – MRC grant no. MR/J006742/1) and gs4:Guy's and St Thomas' Charity (grants R080530 and R090782). SC, IRM, PM, and DSt were also funded by the EU project BIO-DrIM. EN-L was funded by a scholarship from CONICYT Bicentennial Becas-Chile, Chile. MPH-F has also received funding from the European Union, Seventh Framework Programme [FP7/2007–2013], under grant agreement no HEALTH-F5–2010–260687: The ONE Study. The research was funded/supported by the gs9:National Institute for Health ResearchBiomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and Kings College London.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mark, Dr Patrick
Authors: Christakoudi, S., Runglall, M., Mobillo, P., Rebollo-Mesa, I., Tsui, T.-L., Nova-Lamperti, E., Norris, S., Kamra, Y., Hilton, R., Bhandari, S., Baker, R., Berglund, D., Carr, S., Game, D., Griffin, S., Kalra, P. A., Lewis, R., Mark, P. B., Marks, S. D., MacPhee, I., McKane, W., Mohaupt, M. G., Pararajasingam, R., Kon, S. P., Serón, D., Sinha, M., Tucker, B., Viklický, O., Lechler, R. I., Lord, G. M., Stahl, D., and Hernandez-Fuentes, M. P.
Subjects:R Medicine > RC Internal medicine
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Molecular and Cellular Endocrinology
Publisher:Elsevier
ISSN:0303-7207
ISSN (Online):1872-8057
Published Online:07 February 2018
Copyright Holders:Copyright © 2018 Elsevier B.V.
First Published:First published in Molecular and Cellular Endocrinology 473: 205-216
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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