Hepatic Gene Expression Profiles Differentiate Steatotic and Non-steatotic Grafts in Liver Transplant Recipients

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F19%3A00077897" target="_blank" >RIV/00023001:_____/19:00077897 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/19:10399139 RIV/00064165:_____/19:10399139

Result on the web

<a href="https://www.frontiersin.org/articles/10.3389/fendo.2019.00270/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fendo.2019.00270/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fendo.2019.00270" target="_blank" >10.3389/fendo.2019.00270</a>

Result language

angličtina

Original language name

Hepatic Gene Expression Profiles Differentiate Steatotic and Non-steatotic Grafts in Liver Transplant Recipients

Original language description

Background: Liver transplantation leads to non-alcoholic fatty liver disease or nonalcoholic steatohepatitis in up to 40% of graft recipients. The aim of our study was to assess transcriptomic profiles of liver grafts and to contrast the hepatic gene expression between the patients after transplantation with vs. without graft steatosis. Methods: Total RNA was isolated from liver graft biopsies of 91 recipients. Clinical characteristics were compared between steatotic (n = 48) and control (n = 43) samples. Their transcriptomic profiles were assessed using Affymetrix HuGene 2.1 ST Array Strips processed in Affymetrix GeneAtlas. Data were analyzed using Partek Genomics Suite 6.6 and Ingenuity Pathway Analysis. Results: The individuals with hepatic steatosis showed higher indices of obesity including weight, waist circumference or BMI but the two groups were comparable in measures of insulin sensitivity and cholesterol concentrations. We have identified 747 transcripts (326 upregulated and 421 downregulated in steatotic samples compared to controls) significantly differentially expressed between grafts with vs. those without steatosis. Among the most downregulated genes in steatotic samples were P4HA1, IGF1, or fetuin B while the most upregulated were PLIN1 and ME1. Most influential upstream regulators included HNF1A, RXRA, and FXR. The metabolic pathways dysregulated in steatotic liver grafts comprised blood coagulation, bile acid synthesis and transport, cell redox homeostasis, lipid and cholesterol metabolism, epithelial adherence junction signaling, amino acid metabolism, AMPK and glucagon signaling, transmethylation reactions, and inflammation-related pathways. The derived mechanistic network underlying major transcriptome differences between steatotic samples and controls featured PPARA and SERPINE1 as main nodes. Conclusions: While there is a certain overlap between the results of the current study and published transcriptomic profiles of non-transplanted livers with steatosis, we have identified discrete characteristics of the non-alcoholic fatty liver disease in liver grafts potentially utilizable for the establishment of predictive signature.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30219 - Gastroenterology and hepatology

Project

<a href="/en/project/NV15-26906A" target="_blank" >NV15-26906A: Genetic, transcriptomic and metabolic profiles of patients after liver transplantation with respect to the development of NAFLD/NASH.</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

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

Name of the periodical

Frontiers in endocrinology [online]

ISSN

1664-2392

e-ISSN

—

Volume of the periodical

10

Issue of the periodical within the volume

April 30

Country of publishing house

CH - SWITZERLAND

Number of pages

11

Pages from-to

"art. no. 270"

UT code for WoS article

000466580500001

EID of the result in the Scopus database

2-s2.0-85065472968