Cheng Chew W, Pedicini Lucia, Alcala Cintli Morales, Deligianni Fenia, Smith Jessica, Murray Ryan D, Todd Harriet J, Forde Niamh, McKeown Lynn
University of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UK.
Biochem Biophys Rep. 2025 Feb 15;41:101944. doi: 10.1016/j.bbrep.2025.101944. eCollection 2025 Mar.
is an evolutionarily conserved protein that encodes for the Rab GTPase Rab46, and the CRAC channel modulator, CRACR2A. Previous genome wide association studies have demonstrated the association of variants in the progression of non-alcoholic fatty liver disease (NAFLD). In this study we show that mice with global depletion of have significantly larger livers than their wild-type (WT) counterparts. We performed RNA-sequencing (RNA-seq) analysis of liver tissues to investigate differential global gene expression among and WT mice. Of the 69 differentially expressed genes (DEGs), analyses of biological processes found significant enrichment in liver and bile development, with 6 genes ( and ) involved in both processes. Specific consideration of possible roles of DEGs or their products in NAFLD progression to (NASH) and hepatocarcinoma (HCC), demonstrated DEGs in the livers of mice had roles in molecular pathways including lipid metabolism, inflammation, ER stress and fibrosis. The results in this study provide additional insights into molecular mechanisms responsible for increasing susceptibility of liver injuries associated with .
是一种进化保守蛋白，编码Rab GTP酶Rab46以及CRAC通道调节剂CRACR2A。先前的全基因组关联研究已证明非酒精性脂肪性肝病（NAFLD）进展中变异体的关联。在本研究中，我们表明全局缺失该蛋白的小鼠肝脏明显大于其野生型（WT）对照。我们对肝脏组织进行了RNA测序（RNA-seq）分析，以研究该蛋白缺失小鼠和WT小鼠之间的差异全局基因表达。在69个差异表达基因（DEG）中，生物学过程分析发现肝脏和胆汁发育有显著富集，有6个基因（具体基因未给出）参与这两个过程。对DEG或其产物在NAFLD进展为非酒精性脂肪性肝炎（NASH）和肝癌（HCC）中可能作用的具体考虑表明，该蛋白缺失小鼠肝脏中的DEG在包括脂质代谢、炎症、内质网应激和纤维化等分子途径中起作用。本研究结果为与该蛋白相关的肝脏损伤易感性增加的分子机制提供了更多见解。
