Gene Expression Changes Associated with the Loss of Heterogeneous Nuclear Ribonucleoprotein M Function

• 作者: Akiko Sakasai-Sakai Jun-ichi Takino Kentaro Nagamine Masayoshi Takeuchi Mikoto Suzuki Takamitsu Hori
• 来源期刊: 美国分子生物学期刊(英文)
• 学科: 医学
• 关键词: Glycation NONALCOHOLIC STEATOHEPATITIS HETEROGENEOUS Nuclear RIBONUCLEOPROTEIN M Biomarkers
• 年，卷（期）: 2017,（2）
• 页码范围: 87-98
• 页数: 12页
• 分类号: R73

摘要

Advanced glycation endproducts (AGEs) are formed by the nonenzymatic reaction of sugars with proteins. Glycation may adversely affect proteins, such as by inducing a loss of function. It has been shown that glyceraldehyde-derived AGEs (Glycer-AGEs) accumulate in the liver of patients with nonalcoholic steatohepatitis (NASH). Previously, we showed the formation of intracellular Glycer-AGEs upon exposure of hepatocytes to fructose in vitro, and identified an RNA-binding protein, heterogeneous nuclear ribonucleoprotein M (HNRNPM), as a target for glycation. However, the impact of glycated HNRNPM in NASH remains poorly understood. In this study, we examined gene expression changes caused by HNRNPM knockdown, and investigated the up- and down-regulated genes as noninvasive biomarker candidates for NASH. Microarray analysis after HNRNPM knockdown showed that the levels of 138 transcripts were increased, while those of 100 transcripts were decreased as compared with those in the control. Gene Ontology-based functional analysis showed that 14 upregulated and 9 downregulated genes were associated with the extracellular space, which may enable their detection using blood tests. Among these, six of the up- and down-regulated genes were associated with the extracellular exosome. These results suggest that the loss of HNRNPM function by glycation is reflected extracellularly. Therefore, the identified genes may serve as noninvasive biomarkers for Glycer-AGEs-related NASH.