多房棘球蚴感染小鼠肝转录组分析及肝纤维化关键基因的筛选与验证OA北大核心CSTPCD

In order to explore the key gene changes in host liver fibrosis caused by Echinococcus multilocularis larvae infection,a mouse model of E.multilocularis larvae infection was established,and high-throughput sequencing technology was utilized to obtain mRNA expression profiles of the liver at different time points following infection with E.multilocularis larvae.Combined with DisGeNET,GeneGards and other databases,gene sets related to liver fibrosis were minded to explore the important genes affecting liver fibrosis during infection.The results showed that collagen fiber deposition occurred in the livers of mice infected with E.multilocularis larvae.Transcriptome sequencing,combined with the vlookup function for data retrieval,revealed that 2 943 liver fibrosis-related genes were differentially expressed at different times during the E.multilocularis larvae infection.Among them,genes showing significant up-regulation were predominantly enriched in PI3K-Akt and other pathways.The results of real-time fluorescence quantitative PCR were consistent with those of high-throughput sequencing.In the pathway,the expression levels of nerve growth factor(Ngf)and Tenascin C(Tnc)genes were higher in hepatic stellate cells compared to hepatic parenchymal cells,hepatic sinusoidal endothelial cells and Kupffer cells.Knockdown of Ngf gene in mouse primary hepatic stellate cells affected the expression of collagen genes Col1α1 and Timp1,indicating that these pathways and genes might play roles in the development of liver fibrosis in mice following E.multilocularis infection.