title: Gene Expression Profile in the Liver of BALB/c Mice Infected with Fasciola hepatica.
abstract: BACKGROUND
  Fasciola hepatica infection still remains one of the helminthic neglected tropical diseases (NTDs). It has a huge worldwide distribution, affecting mainly cattle and, sometimes, human beings. In addition to data reported about the immunological response induced by helminthic infections and that induced by Fasciola hepatica, little is known about the gene expression profile in its organ target, the liver, which is where adult worms are established and live for long periods of time, causing its characteristic pathology. In the present work, we study both the early and late gene expression profiles in the livers of mice infected with F. hepatica metacercariae using a microarray-based methodology.
  
  
  METHODS
  A total of 9 female-6-week-old BALB/c mice (Charles River Laboratories, Barcelona, Spain) weighing 20 to 35 g were used for the experiments. Two groups of BALB/c mice were orally infected with seven F. hepatica metacercariae, and the other group remained untreated and served as a control. Mice were humanely euthanized and necropsied for liver recovery, histological assessment of hepatic damage, RNA isolation, microarray design and gene expression analysis on the day of infection (t0), seven days post-infection (t7) and twenty-one days post-infection (t21).
  
  
  RESULTS
  We found that F. hepatica infection induces the differential expression of 128 genes in the liver in the early stage of infection and 308 genes in the late stage, and most of them are up-regulated. The Ingenuity Pathway Analysis revealed significant changes in the pathways related to metabolism, biosynthesis and signaling as well as genes implicated in inducing liver-toxicity, injury and death.
  
  
  CONCLUSIONS
  The present study provides us insights at the molecular level about the underlying mechanisms used by F. hepatica, leading to liver damage and its subsequent pathophysiology. The expression pattern obtained here could also be used to explain the lack of association between infection with F. hepatica and cholangiocarcinoma. However, more studies should be performed to confirm this hypothesis.
authors.affiliation: Instituto de Investigación Biomédica de Salamanca-Centro de Investigación de Enfermedades Tropicales de la Universidad de Salamanca (IBSAL-CIETUS), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Castilla y León, España.
authors.forename: Jose
authors.initials: J
authors.lastname: Rojas-Caraballo
authors.affiliation: Instituto de Investigación Biomédica de Salamanca-Centro de Investigación de Enfermedades Tropicales de la Universidad de Salamanca (IBSAL-CIETUS), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Castilla y León, España.
authors.forename: Julio
authors.initials: J
authors.lastname: López-Abán
authors.affiliation: Instituto de Investigación Biomédica de Salamanca-Centro de Investigación de Enfermedades Tropicales de la Universidad de Salamanca (IBSAL-CIETUS), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Castilla y León, España.
authors.forename: Pedro
authors.initials: P
authors.lastname: Fernández-Soto
authors.affiliation: Instituto de Investigación Biomédica de Salamanca-Centro de Investigación de Enfermedades Tropicales de la Universidad de Salamanca (IBSAL-CIETUS), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Castilla y León, España.
authors.forename: Belén
authors.initials: B
authors.lastname: Vicente
authors.affiliation: Departamento de Anatomía e Histología Humanas, Facultad de Medicina, Universidad de Salamanca, Salamanca, Castilla y León, España.
authors.forename: Francisco
authors.initials: F
authors.lastname: Collía
authors.affiliation: Instituto de Investigación Biomédica de Salamanca-Centro de Investigación de Enfermedades Tropicales de la Universidad de Salamanca (IBSAL-CIETUS), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Castilla y León, España.
authors.forename: Antonio
authors.initials: A
authors.lastname: Muro
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005210:Fasciola hepatica / Q000254:growth & development* / Q000472:pathogenicity; D005211:Fascioliasis / Q000235:genetics* / Q000469:parasitology / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006790:Host-Parasite Interactions; D008099:Liver / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D058488:Metacercariae / Q000254:growth & development* / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D058977:Molecular Sequence Annotation