A serum-induced gene signature in hepatocytes is associated with pediatric nonalcoholic fatty liver disease.
A serum-induced gene signature in hepatocytes is associated with pediatric nonalcoholic fatty liver disease.
复制标题
肝细胞中血清诱导的基因特征与儿童非酒精性脂肪肝相关。
DOI：
10.1002/jpn3.12163
复制
发表时间：
2024
影响因子：
2.9
通讯作者：
Salzman,NitaH
中科院分区：
文献类型：
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作者：
HangNghiem-Rao,T;Johnson,JethroS;Pan,Amy;Atkinson,SamanthaN;Behling,Cynthia;Simpson,PippaM;Holtz,MaryL;Weinstock,GeorgeM;Schwimmer,JeffreyB;Salzman,NitaH
儿童非酒精性脂肪性肝病（NAFLD）是一个日益严重的问题，但其潜在机制知之甚少。我们使用转录组报告细胞检测，以探讨在肝细胞报告细胞的血清与非NAFLD.MethodsWe研究了45名儿童NAFLD和28名儿童非NAFLD的血清样品中诱导的转录签名的差异。使用血清诱导培养的HepaRG细胞中的基因表达，并使用RNA测序测定基因表达。计算技术被用来比较基因的表达patterns.ResultsSera从儿童NAFLD诱导的195个基因的表达，显着差异表达的肝细胞相比，控制肥胖。NAFLD与促进炎症、胶原合成和细胞外基质重塑的基因表达增加有关。此外，有较低的表达基因参与内源性和外源性代谢，下调过氧化物酶体功能，氧化磷酸化，外源性，胆汁酸和脂肪酸代谢。一个13基因签名，包括上调TREM1和MMP 1和下调CYP2C9，始终与所有诊断类别的儿童NAFLD.ConclusionThe细胞外环境的血清NAFLD儿童诱导特异性基因谱可区分的肝细胞报告系统。循环因子可能导致炎症和细胞外基质重塑，并损害儿科NAFLD的外源性和内源性代谢。
ObjectivePediatric 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.MethodsWe 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.ResultsSera 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 ofTREM1andMMP1and downregulation ofCYP2C9, was consistently associated with all diagnostic categories of pediatric NAFLD.ConclusionThe 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.