Differential expression of miRNAs in the visceral adipose tissue of patients with non-alcoholic fatty liver disease
Differential expression of miRNAs in the visceral adipose tissue of patients with non-alcoholic fatty liver disease
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DOI：
10.1111/j.1365-2036.2010.04366.x
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发表时间：
2010-08-01
影响因子：
7.6
通讯作者：
Younossi, Z. M.
中科院分区：
文献类型：
--
作者：
Estep, M.;Armistead, D.;Younossi, Z. M.
内脏脂肪组织（VAT）分泌的可溶性分子可促进非酒精性脂肪性肝病（NAFLD）的进展。microRNAs（miRNAs）可能调控NAFLD发病机制中的某些分子通路，目的研究miRNAs在NAFLD患者内脏脂肪组织中的表达。将活检证实的NAFLD患者分为非酒精性脂肪性肝炎（NASH）（n = 12）和非NASH（n = 12）队列，对照临床和人口统计学特征。提取的总RNA使用TaqMan Human MicroRNA阵列进行分析。结果113条miRNA在NASH患者和非NASH患者中差异表达（P <0. 05）。其中，7个在多重检验校正后仍然显著（hsa-miR-132、hsa-miR-150、hsa-miR-433、hsa-miR-28- 3 p、hsa-miR-511、hsa-miR-517 a、hsa-miR-671）。这些miRNAs的预测靶基因包括胰岛素受体途径组分（IGF 1、IGFR 13）、细胞因子（CCL 3、IL 6）、ghrelin/obestatin基因和炎症相关基因（NFKB 1、RELB、FAS）。此外，两种miRNA种类hsa-miR-197和hsa-miR-99与NASH患者的细胞周围纤维化显著相关（P < 0.05）。血清中IL-6水平与所有7种能够下调IL-6编码基因的miRNAs表达水平呈负相关。结论VAT中的miRNAs表达可能与NAFLD的发病机制有关-这一发现可以将相对简单的脂肪变性与NASH区分开来。这可能有助于确定药物治疗方案的潜在靶点和NASH的候选生物标志物。
P>BackgroundProgression of non-alcoholic fatty liver disease (NAFLD) can be facilitated by soluble molecules secreted by visceral adipose tissue (VAT). MicroRNAs (miRNAs) are likely to regulate some of these molecular pathways involved in pathogenesis of NAFLD.AimTo profile miRNA expression in the visceral adipose tissue of patients with NAFLD.MethodsVisceral adipose tissue samples were collected from NAFLD patients and frozen. Patients with biopsy-proven NAFLD were divided into non-alcoholic steatohepatitis (NASH) (n = 12) and non-NASH (n = 12) cohorts controlled for clinical and demographic characteristics. Extracted total RNA was profiled using TaqMan Human MicroRNA arrays. Univariate Mann-Whitney comparisons and multivariate regression analysis were performed to compare miRNA profiles.ResultsA total of 113 miRNA differentially expressed between NASH patients and non-NASH patients (P < 0.05). Of these, seven remained significant after multiple test correction (hsa-miR-132, hsa-miR-150, hsa-miR-433, hsa-miR-28-3p, hsa-miR-511, hsa-miR-517a, hsa-miR-671). Predicted target genes for these miRNAs include insulin receptor pathway components (IGF1, IGFR13), cytokines (CCL3, IL6), ghrelin/obestatin gene, and inflammation-related genes (NFKB1, RELB, FAS). In addition, two miRNA species, hsa-miR-197 and hsa-miR-99, were significantly associated with pericellular fibrosis in NASH patients (P < 0.05). Levels of IL-6 in the serum negatively correlated with the expression levels of all seven miRNAs capable of down regulating IL-6 encoding gene.ConclusionsmiRNA expression from VAT may contribute to the pathogenesis of NAFLD - a finding which may distinguish relatively simple steatosis from NASH. This could help identify potential targets for pharmacological treatment regimens and candidate biomarkers for NASH.