Hepatic gene expression profile in mice perorally infected with Echinococcus multilocularis eggs.

Autor: Bruno Gottstein, Matthias Wittwer, Marc Schild, Michael Merli, Stephen L Leib, Norbert Müller, Joachim Müller, Rolf Jaggi
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: PLoS ONE, Vol 5, Iss 4, p e9779 (2010)
Druh dokumentu: article
ISSN: 1932-6203
40756742
DOI: 10.1371/journal.pone.0009779
Popis: BACKGROUND: Alveolar echinococcosis (AE) is a severe chronic hepatic parasitic disease currently emerging in central and eastern Europe. Untreated AE presents a high mortality (>90%) due to a severe hepatic destruction as a result of parasitic metacestode proliferation which behaves like a malignant tumor. Despite this severe course and outcome of disease, the genetic program that regulates the host response leading to organ damage as a consequence of hepatic alveolar echinococcosis is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used a mouse model of AE to assess gene expression profiles in the liver after establishment of a chronic disease status as a result of a primary peroral infection with eggs of the fox tapeworm Echinococcus multilocularis. Among 38 genes differentially regulated (false discovery rate adjusted p, while 3 associated with the functional group . Upregulated genes associated with could be clustered into functional subgroups including , , , and . Two downregulated genes related to and , respectively. The genes either associated with an or an pathway. From the overexpressed genes, 18 genes were subsequently processed with a Custom Array microfluidic card system in order to assess respective expression status at the mRNA level relative to 5 reference genes (Gapdh, Est1, Rlp3, Mdh-1, Rpl37) selected upon a constitutive and stable expression level. The results generated by the two independent tools used for the assessment of gene expression, i.e., microarray and microfluidic card system, exhibited a high level of congruency (Spearman correlation rho = 0.81, p = 7.87e-5) and thus validated the applied methods. CONCLUSIONS/SIGNIFICANCE: Based on this set of biomarkers, new diagnostic targets have been made available to predict disease status and progression. These biomarkers may also offer new targets for immuno-therapeutic intervention.
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