Genome wide transcriptomics analyses of livers reveal induction of N-glycosylation upon loss of nuclear receptors FXR and SHP

We performed high-throughput RNA-sequencing on livers from hepatocyte specific Fxr-/- Shp-/- double knockout mice, and identified upregulation of N-glycan protein modification machinery. This correlated positively with Golgi structural defects and alterations in the hepatic secretome. This study identifies a new role for hepatic FXR-SHP axis in Golgi dynamics and N-glycosylation, apart from its traditional function in nutrient metabolism. Hepatic mRNA expression profiles of adult fl/fl Fxr fl/fl Shp and hepatocyte specific Fxr-/- Shp-/- (n=3) male mice.本研究对肝细胞特异性Fxr敲除、Shp敲除的双基因敲除小鼠的肝脏组织开展高通量RNA测序（high-throughput RNA-sequencing），鉴定得到N-聚糖蛋白质修饰系统（N-glycan protein modification machinery）的表达上调。该上调现象与高尔基体结构缺陷及肝脏分泌组（hepatic secretome）的改变呈正相关。本研究揭示了肝脏FXR-SHP信号轴（FXR-SHP axis）在高尔基体动态平衡（Golgi dynamics）与N-糖基化（N-glycosylation）中的全新功能，补充了其在营养代谢之外的传统生理作用。本次数据集包含成年fl/fl Fxr fl/fl Shp雄性小鼠与肝细胞特异性Fxr敲除、Shp敲除的雄性小鼠（每组n=3）的肝脏mRNA表达谱（hepatic mRNA expression profiles）。