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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F18%3A00077191" target="_blank" >RIV/00023001:_____/18:00077191 - isvavai.cz</a>

Výsledek na webu

<a href="https://reader.elsevier.com/reader/sd/pii/S0303720718300443?token=D1542D61A1DF4DD24754064318927E2E6319B36DCC625279BDD4AD216C237593CC86C6CB0778A3BF7E081AF26DE661E5" target="_blank" >https://reader.elsevier.com/reader/sd/pii/S0303720718300443?token=D1542D61A1DF4DD24754064318927E2E6319B36DCC625279BDD4AD216C237593CC86C6CB0778A3BF7E081AF26DE661E5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.mce.2018.01.021" target="_blank" >10.1016/j.mce.2018.01.021</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with &quot;operational tolerance&quot; 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with &quot;operational tolerance&quot; 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30213 - Transplantation

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular and cellular endocrinology

ISSN

0303-7207

e-ISSN

—

Svazek periodika

473

Číslo periodika v rámci svazku

September 15

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

205-216

Kód UT WoS článku

000447981900020

EID výsledku v databázi Scopus

2-s2.0-85042348735