Schistosomiasis japonica remains a significant public health problem in China and Southeast Asian countries. The most typical and serious outcome of the chronic oriental
schistosomiasis is the progressive
granuloma and
fibrosis in the host liver, which has been a major medical challenge. However, the molecular mechanism underling the hepatic pathogenesis is still not clear.
METHODOLOGY AND PRINCIPAL FINDINGS: Using microarrays, we quantified the temporal gene expression profiles in the liver of Schistosoma japonicum-infected BALB/c mice at 15, 30, and 45 day post
infection (dpi) with that from uninfected mice as controls. Gene expression alternation associated with liver damage was observed in the initial phase of
infection (dpi 15), which became more magnificent with the onset of egg-laying. Up-regulated genes were dominantly associated with inflammatory infiltration, whereas down-regulated genes primarily led to the hepatic functional disorders. Simultaneously,
microRNA profiles from the same samples were decoded by Solexa sequencing. More than 130
miRNAs were differentially expressed in murine liver during S. japonicum
infection.
MiRNAs significantly dysregulated in the mid-phase of
infection (dpi 30), such as mmu-miR-146b and mmu-miR-155, may relate to the regulation of hepatic inflammatory responses, whereas
miRNAs exhibiting a peak expression in the late phase of
infection (dpi 45), such as
mmu-miR-223, mmu-miR-146a/b, mmu-miR-155, mmu-miR-34c, mmu-miR-199, and
mmu-miR-134, may represent a molecular signature of the development of schistosomal hepatopathy. Further, a dynamic
miRNA-gene co-expression network in the progression of
infection was constructed.
CONCLUSIONS AND SIGNIFICANCE: This study presents a global view of dynamic expression of both
mRNA and
miRNA transcripts in murine liver during S. japonicum
infection, and highlights that
miRNAs may play a variety of regulatory roles in balancing the immune responses during the development of hepatic pathology. The data provide robust information for further researches on the pathogenesis and molecular events of hepatopathy induced by schistosome eggs.