title: Time course of gene expression profiling in the liver of experimental mice infected with Echinococcus multilocularis.
abstract: BACKGROUND
  Alveolar echinococcosis (AE) is a severe chronic parasitic disease which behaves like a slow-growing liver cancer. Clinical observations suggest that the parasite, Echinococcus multilocularis (E. multilocularis) influences liver homeostasis and hepatic cell metabolism. However, this has never been analyzed during the time course of infection in the common model of secondary echinococcosis in experimental mice.
  
  
  RESULTS
  Gene expression profiles were assessed using DNA microarray analysis, 1, 2, 3 and 6 months after injection of E. multilocularis metacestode in the liver of susceptible mice. Data were collected at different time points to monitor the dynamic behavior of gene expression. 557 differentially expressed genes were identified at one or more time points, including 351 up-regulated and 228 down-regulated genes. Time-course analysis indicated, at the initial stage of E. multilocularis infection (month 1-2), that most of up-regulated pathways were related to immune processes and cell trafficking such as chemokine-, mitogen-activated protein kinase (MAPK) signaling, and down-regulated pathways were related to xenobiotic metabolism; at the middle stage (month 3), MAPK signaling pathway was maintained and peroxisome proliferator-activated receptor (PPAR) signaling pathway emerged; at the late stage (month 6), most of up-regulated pathways were related to PPAR signaling pathway, complement and coagulation cascades, while down-regulated pathways were related to metabolism of xenobiotics by cytochrome P450. Quantitative RT-PCR analysis of a random selection of 19 genes confirmed the reliability of the microarray data. Immunohistochemistry analysis showed that proliferating cell nuclear antigen (PCNA) was increased in the liver of E. multilocularis infected mice from 2 months to 6 months.
  
  
  CONCLUSIONS
  E. multilocularis metacestode definitely exerts a deep influence on liver homeostasis, by modifying a number of gene expression and metabolic pathways. It especially promotes hepatic cell proliferation, as evidenced by the increased PCNA constantly found in all the experimental time-points we studied and by an increased gene expression of key metabolic pathways.
authors.affiliation: Xinjiang Key Laboratory of Echinococcosis and Medical Research Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
authors.forename: Renyong
authors.initials: R
authors.lastname: Lin
authors.forename: Guodong
authors.initials: G
authors.lastname: Lü
authors.forename: Junhua
authors.initials: J
authors.lastname: Wang
authors.forename: Chuanshan
authors.initials: C
authors.lastname: Zhang
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Xie
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Lu
authors.forename: Georges
authors.initials: G
authors.lastname: Mantion
authors.forename: Hélène
authors.initials: H
authors.lastname: Martin
authors.forename: Lysiane
authors.initials: L
authors.lastname: Richert
authors.forename: Dominique A
authors.initials: DA
authors.lastname: Vuitton
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004443:Echinococcosis / Q000235:genetics* / Q000382:microbiology; D048210:Echinococcus multilocularis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007109:Immunity / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System