A serum-induced gene signature in hepatocytes is associated with pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 2024 Apr;78(4):886-897
Date
02/23/2024Pubmed ID
38390691DOI
10.1002/jpn3.12163Scopus ID
2-s2.0-85189912724 (requires institutional sign-in at Scopus site)Abstract
OBJECTIVE: Pediatric nonalcoholic fatty liver disease (NAFLD) is a growing problem, but its underlying mechanisms are poorly understood. We used transcriptomic reporter cell assays to investigate differences in transcriptional signatures induced in hepatocyte reporter cells by the sera of children with and without NAFLD.
METHODS: We studied serum samples from 45 children with NAFLD and 28 children without NAFLD. The sera were used to induce gene expression in cultured HepaRG cells and RNA-sequencing was used to determine gene expression. Computational techniques were used to compare gene expression patterns.
RESULTS: Sera from children with NAFLD induced the expression of 195 genes that were significantly differentially expressed in hepatocytes compared to controls with obesity. NAFLD was associated with increased expression of genes promoting inflammation, collagen synthesis, and extracellular matrix remodeling. Additionally, there was lower expression of genes involved in endobiotic and xenobiotic metabolism, and downregulation of peroxisome function, oxidative phosphorylation, and xenobiotic, bile acid, and fatty acid metabolism. A 13-gene signature, including upregulation of TREM1 and MMP1 and downregulation of CYP2C9, was consistently associated with all diagnostic categories of pediatric NAFLD.
CONCLUSION: The extracellular milieu of sera from children with NAFLD induced specific gene profiles distinguishable by a hepatocyte reporter system. Circulating factors may contribute to inflammation and extracellular matrix remodeling and impair xenobiotic and endobiotic metabolism in pediatric NAFLD.
Author List
Hang Nghiem-Rao T, Johnson JS, Pan A, Atkinson SN, Behling C, Simpson PM, Holtz ML, Weinstock GM, Schwimmer JB, Salzman NHAuthors
Samantha N. Atkinson PhD Bioinformatics Analyst III in the Microbiology and Immunology department at Medical College of WisconsinT Hang Nghiem-Rao MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Cells, CulturedChild
Hepatocytes
Humans
Inflammation
Liver
Non-alcoholic Fatty Liver Disease
Xenobiotics
