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

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Title: Steroid regulation: an overlooked aspect of tolerance and chronic rejection in kidney transplantation
Author(s): 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, PA
Lewis, R
Mark, PB
Marks, SD
Macphee, I
McKane, W
Mohaupt, MG
Pararajasingam, R
Phin Kon, S
Serón, D
Sinha, M
Tucker, B
Viklický, O
Lechler, RI
Lord, GM
Stahl, D
Hernandez-Fuentes, MP
Item Type: Journal Article
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.
Publication Date: 15-Sep-2018
Date of Acceptance: 29-Jan-2018
URI: http://hdl.handle.net/10044/1/57247
DOI: https://dx.doi.org/10.1016/j.mce.2018.01.021
ISSN: 0303-7207
Publisher: Elsevier
Start Page: 205
End Page: 216
Journal / Book Title: Molecular and Cellular Endocrinology
Volume: 473
Copyright Statement: © 2018 Elsevier B.V. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Chronic rejection
Kidney
Steroid conversion
Steroid receptor genes
Tolerance
Transplantation
06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Endocrinology & Metabolism
Publication Status: Published
Online Publication Date: 2018-02-07
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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