RNAseq analysis reveals transcriptome changes associated with the progression of non-alcoholic liver disease in livers from Efcab4b knockout mice
RNAseq analysis reveals transcriptome changes associated with the progression of non-alcoholic liver disease in livers from Efcab4b knockout mice
ABSTRACT EFCAB4B 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 EFCAB4B variants in the progression of non-alcoholic liver disease (NAFLD). In this study we show that mice with global depletion of Efcab4b-/- 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 Efcab4b-/-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 (Pck1, Aacs, Onecut1, E2f8, Xbp1, and Hes1) 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 Efcab4b-/- 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 EFCAB4B.
Cheng Chew W.、Morales Alcala Cintli、Deligianni Fenia、Forde Niamh、Pedicini Lucia、McKeown Lynn、Smith Jessica
University of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic MedicineUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic MedicineUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic MedicineUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic MedicineUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic MedicineUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic MedicineUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine
基础医学分子生物学生物科学研究方法、生物科学研究技术
human EFCAB4B (Rab46 / CRACR2A)mouse Efcab4blivernon-alcoholic liver disease (NAFLD)non-alcoholic steatohepatitis (NASH)hepatocarcinoma (HCC)
Cheng Chew W.,Morales Alcala Cintli,Deligianni Fenia,Forde Niamh,Pedicini Lucia,McKeown Lynn,Smith Jessica.RNAseq analysis reveals transcriptome changes associated with the progression of non-alcoholic liver disease in livers from Efcab4b knockout mice[EB/OL].(2025-03-28)[2025-05-03].https://www.biorxiv.org/content/10.1101/2024.05.13.593681.点此复制
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