儿童非酒精性脂肪性肝病中外泌体微小RNA谱及其与转氨酶和尿酸的相关性

Exosomal miRNAs Profile in Children's Nonalcoholic Fatty Liver Disease and the Correlation with Transaminase and Uric Acid.

作者信息

Zhou Xuelian, Huang Ke, Jia Junjun, Ni Yan, Yuan Jinna, Liang Xinyi, Lin Hu, Peng Wei, Wu Wei, Dong Guanping, Fu Junfen

机构信息

Division of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University, College of Medicine, Hangzhou, China.

出版信息

Ann Nutr Metab. 2020;76(1):44-53. doi: 10.1159/000506665. Epub 2020 Mar 13.

DOI:10.1159/000506665

PMID:32172249

Abstract

OBJECTIVE

The incidence of non-alcoholic fatty liver disease (NAFLD) in children increased rapidly. However, the pathogenesis of NAFLD, especially how non-alcoholic fatty liver progress to non-alcoholic steatohepatitis, is still unclear. This study aims to explore the exosomal miRNAs profiles and the underline pathogenesis of child NAFLD.

METHODS

Twenty NAFLD and 20 health control were enrolled in this study. Circulating exosomes were isolated, and RNA sequencing was performed in test set (3 NAFLD/3 Controls). The differentially expressed miRNAs (DEM) were further validated in validation set (17 NAFLD/17 Controls). Spearman correlation -analysis was used to investigate the association between DEM and clinical parameters.

RESULTS

Eighty-two miRNAs were differentially expressed (absolute fold change >2 and p < 0.05) in the 2 groups, they were involved in fat acid metabolism, starch and sucrose metabolism, bile acid metabolism and inflammation. miRNA122-5p, miRNA34a-5p, -miRNA155-5p and miRNA146b-3p were up-regulated in NAFLD group (p < 0.05) and positively correlated with body mass index (r, 0.41-0.59), alanine aminotransferase (r, 0.36-0.52), aspartate transaminase (r, 0.31-0.48) and uric acid (UA, r, 0.51-0.69; p < 0.05).

CONCLUSIONS

Circulating exosomal miRNAs may be involved in the pathogenesis of NAFLD and correlated with transaminase and UA.

摘要

目的

儿童非酒精性脂肪性肝病（NAFLD）的发病率迅速上升。然而，NAFLD的发病机制，尤其是非酒精性脂肪肝如何进展为非酒精性脂肪性肝炎，仍不清楚。本研究旨在探讨儿童NAFLD的外泌体miRNA谱及其潜在发病机制。

方法

本研究纳入20例NAFLD患儿和20例健康对照。分离循环外泌体，并在测试组（3例NAFLD/3例对照）中进行RNA测序。差异表达的miRNA（DEM）在验证组（17例NAFLD/17例对照）中进一步验证。采用Spearman相关性分析研究DEM与临床参数之间的关联。

结果

两组中有82个miRNA差异表达（绝对变化倍数>2且p<0.05），它们参与脂肪酸代谢、淀粉和蔗糖代谢、胆汁酸代谢及炎症反应。miRNA122-5p、miRNA34a-5p、miRNA155-5p和miRNA146b-3p在NAFLD组中上调（p<0.05），并与体重指数（r，0.41-0.59）、丙氨酸氨基转移酶（r，0.36-0.52）、天冬氨酸氨基转移酶（r，0.31-0.48）和尿酸（UA，r，0.51-0.69；p<0.05）呈正相关。