Unknown,Transcriptomics,Genomics,Proteomics

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MicroRNA-gene expression network in murine liver during Schistosoma japonicum infection

ABSTRACT: 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 mechanisms that underlie the hepatic pathogenesis induced by schistosomal egg deposition have not yet been well-defined. Using microarrays, we quantified the temporal gene expression profiles in the liver of Schistosoma japonicum-infected BALB/c mice at day 15, 30, and 45 post infection (pi) with that from uninfected mice as controls. Meanwhile, microRNA expression profiles from the same samples were decoded by parallel solexa sequencing. Gene expression alternation associated with liver damage was observed even at early stage of infection (e.g., pi 15), which became more magnificent onset of egg deposition within the liver tissue. Up-regulated genes were dominantly associated with inflammatory infiltration of liver during S. japonicum infection, whereas down-regulated genes primarily led to the hepatic functional disorders. More than 130 miRNAs were differentially expressed during S. japonicum infection, and dynamic miRNA-gene co-expression network has been constructed during the development of hepatic pathology. A four chip study using total RNA recovered from liver tissues of BALB/c mice which were percutaneously infected with 30 Â± 2 cercariae of S. japonicum at day 0, 15, 30, and 45 post infection, respectively.

ORGANISM(S): Mus musculus

SUBMITTER: Pengfei Cai

PROVIDER: E-GEOD-45985 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:In schistosomiasis japonica, the egg-induced granulomatous response and the development of extensive hepatic fibrosis is the main pathology. Information regarding the specific mechanisms associated with granuloma regression and the subsequent recovery events in the host liver are still limited. In this study, a murine model of schistosomiasis japonica was used to characterise the multicellular pathways occurring during liver regeneration. Schistosoma japonicum-infected C57BL/6 mice were administered with the drug praziquantel (PZQ), on a daily basis for five consecutive days to eliminate all adult parasites. The pathological changes of PZQ-treated groups after 3, 6 and 7 weeks post PZQ treatment were examined, along with the assessment of cellular infiltration to the liver. PZQ treatment significantly reduced the degree of splenomegaly, granuloma density and the collagen deposition of liver fibrosis. The infiltration of inflammatory cells, including neutrophils, eosinophils and macrophages to the liver were as well significantly decreased. Transcriptomic analysis revealed the significant up-regulation of fatty acid metabolism genes and the identification of peroxisome proliferator-activated receptor alpha (PPAR-α) as the upstream regulator during the process of liver recovery. Aryl hydrocarbon receptor (AhR) signalling pathway that is involved primarily in the regulation of hepatic enzymes responsible for xenobiotic metabolism was as well differentially up-regulated. These findings indicate that schistosome egg-induced fibrogenesis process is reversible, and provide a better understanding of the regression mechanisms associated with hepatic schistosomiasis. These results hold important implications for the future alleviation of this and other fibrotic diseases of clinical significance. C57BL/6 murine model infected with S. japonicum were treated orally with Praziquantel (PZQ) after 7 weeks post infection to examine the hepatic regression process following drug treatment. These PZQ-treated, non PZQ-treated and uninfected mice were then euthanised at 10, 13, and 14 weeks p.i. Livers were collected from each mice, and subjected to total RNA isolation and gene expression analysis. Microarray analysis of this study was performed using samples derived from 3 individual mice per group/time-point.

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MicroRNA-gene expression network in murine liver during Schistosoma japonicum infection

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