MicroRNA-Gene Expression Network in Murine Liver during Schistosoma japonicum Infection

Abstract

BackgroundSchistosomiasis 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 FindingsUsing 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 SignificanceThis 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.

Dectin-1 is required for miR155 upregulation in murine macrophages in response toCandida albicans

“…Of note, BMDMs interacting with hyphae also increased their levels of other miRNAs, including 125b, miR132, miR199, and miR223. While these miRNAs have been associated with responses to other pathogens 18,[46][47][48] , this is the first report demonstrating their specific induction by C. albicans. Upon activation of a host effector cell by a microbe, miRNAs are induced and commonly act as regulators, modulating the host response.…”

The chronic enteropathogenic disease schistosomiasis

“…124 A broad array of miRNAs in liver was dysregulated and associated with the progression of S. japonicum infection. 125 These results raise the possibility that circulating host miRNAs may be dynamically altered during the course of schistosome infection; this provides an avenue for their development as useful diagnostic and pathogenic biomarkers for schistosomiasis, because of the strong correlation between the expression profile of miRNAs and the status/progression of the disease.…”

Advances in the Diagnosis of Human Schistosomiasis

“…Variations in miRNA profiles during disease progression have been demonstrated in murine models even during very early acute infection (247,248). As the alteration in miRNA expression profiles is often correlated with numerous human diseases, including liver diseases, He et al investigated the serum levels of host miRNAs in mice, rabbits, buffaloes, and humans infected with S. japonicum, and circulating miR-223 was suggested as a potential new biomarker for the detection of schistosome infection and the assessment of the response to chemotherapy (249).…”