Genomic-scale analysis of Pasteurella multocida gene expression during growth within liver tissue of chickens with fowl cholera

We have recently reported the gene expression profile of Pasteurella multocida during growth in the blood of chickens with fowl cholera. Here we report the gene expression profile of P. multocida during growth in the livers of similarly infected chickens. We compared expression profiles of bacteria harvested from the livers of infected chickens with late-stage fowl cholera with those of bacteria grown in rich medium. Independent analysis of bacterial expression profiles from three individual chickens indicated that 93 P. multocida genes were always differentially expressed during growth in liver tissue. Of these 93 genes, 49 were upregulated and 44 downregulated in the host. Many of the upregulated genes were involved in energy production and conversion (9/49) and carbohydrate transport and metabolism (8/49), and a number of these have been shown to be induced under anaerobic conditions in other species. The downregulated genes were generally of unknown or poorly characterised functions (14/44). Comparison of the differentially regulated gene sets identified for growth in liver with those identified previously for growth in blood allowed the identification of a core set of 13 upregulated and 16 downregulated genes that were differentially regulated in at least five of the six infections studied.     

Genomic Analysis Reveals a Potential Role for Cell Cycle Perturbation in HCV-Mediated Apoptosis of Cultured Hepatocytes

The mechanisms of liver injury associated with chronic HCV infection, as well as the individual roles of both viral and host factors, are not clearly defined. However, it is becoming increasingly clear that direct cytopathic effects, in addition to immune-mediated processes, play an important role in liver injury. Gene expression profiling during multiple time-points of acute HCV infection of cultured Huh-7.5 cells was performed to gain insight into the cellular mechanism of HCV-associated cytopathic effect. Maximal induction of cell-death–related genes and appearance of activated caspase-3 in HCV-infected cells coincided with peak viral replication, suggesting a link between viral load and apoptosis. Gene ontology analysis revealed that many of the cell-death genes function to induce apoptosis in response to cell cycle arrest. Labeling of dividing cells in culture followed by flow cytometry also demonstrated the presence of significantly fewer cells in S-phase in HCV-infected relative to mock cultures, suggesting HCV infection is associated with delayed cell cycle progression. Regulation of numerous genes involved in anti-oxidative stress response and TGF-β1 signaling suggest these as possible causes of delayed cell cycle progression. Significantly, a subset of cell-death genes regulated during in vitro HCV infection was similarly regulated specifically in liver tissue from a cohort of HCV-infected liver transplant patients with rapidly progressive fibrosis. Collectively, these data suggest that HCV mediates direct cytopathic effects through deregulation of the cell cycle and that this process may contribute to liver disease progression. This in vitro system could be utilized to further define the cellular mechanism of this perturbation.     

应用基因表达谱芯片研究黄药子对小鼠肝脏的毒性机制(简报)

黄药子为薯蓣科植物黄独(Dioscorea bulbifera L．)的块茎,临床常用于治疗甲状腺肿、抗肿瘤、抗炎、抗病毒等。近年来临床上关于黄药子的毒副作用,尤其是对肝、肾的不良反应屡有报道。当黄药子或其代谢物在肝细胞内累积时会直接干扰肝细