Effect of Activin A and Gpnmb on gene expression in NAFLD/NASH liver in C57BL/6J mice and gene expression change in C57BL/6J mice fed on sugar water-NAFLD/NASH diet compared with standard chow diet. Effect of Activin A and Gpnmb on gene expression in NAFLD/NASH liver in C57BL/6J mice and gene expression change in C57BL/6J mice fed on sugar water-NAFLD/NASH diet compared with standard chow diet

To investigate the mechanism of hepatic Activin A and Gpnmb in NAFLD/NASH, we studied C57BL/6J mice on a FPC NASH diet and sugar water for 16 weeks, compared with standard chow diet, and used adeno-associated viral vectors with a liver-specific thyroxine binding globulin (TBG) promoter to express Activin A or GFP (control), or AAV8-H1-shRNA to knockdown of Gpnmb or scramble control in NAFLD/NASH liver. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different livers in each group. Overall design: Comparative gene expression profiling analysis of RNA-seq data for liver expressed AAV-TBG-GFP (Control) and AAV-TBG-Activin A, AAV8-shRNA SC and AAV8-shRNA Gpnmb on sugar water-FPC NASH diet, as well as liver expressed AAV-TBG-GFP (Control) on standard chow diet.

为探究肝组织激活素A（Activin A）与Gpnmb在非酒精性脂肪性肝病（NAFLD）/非酒精性脂肪性肝炎（NASH）中的作用机制，本研究选取C57BL/6J小鼠，采用FPC NASH膳食结合糖水喂养16周，并以标准维持饲料喂养作为对照；同时使用搭载肝特异性甲状腺素结合球蛋白（TBG）启动子的腺相关病毒（AAV）载体，在NAFLD/NASH模型小鼠肝脏中分别过表达Activin A或绿色荧光蛋白（GFP，对照），或采用AAV8-H1短发夹RNA（shRNA）载体敲低Gpnmb，并以乱序shRNA作为阴性对照。随后，针对每组3只小鼠的肝脏组织开展RNA测序（RNA-seq），并进行基因表达谱分析。
实验整体设计：对糖水-FPC NASH膳食喂养下，分别经肝脏表达AAV-TBG-GFP（对照）、AAV-TBG-Activin A、AAV8-shRNA SC（乱序对照）、AAV8-shRNA-Gpnmb处理的小鼠，以及标准维持饲料喂养且经肝脏表达AAV-TBG-GFP（对照）处理的小鼠，对其肝脏组织的RNA测序数据进行对比基因表达谱分析。