Ex vivo mouse model for hepatic schistosomiasis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64071 | GEO | 2014/12/12
SECONDARY ACCESSION(S): PRJNA270033
REPOSITORIES: GEO
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Project description:An ex vivo approach to studying hepatic schistosomiasis used thick naive mouse liver sections and sterile culturing. This tissue is unfixed, unfrozen, and alive for subsequent in vitro studies. We have cultured and monitored these sections for up to 48 hrs noting unchanged gross hepato-cellular morphology, and no significant increases in hepatotoxicity as demonstrated by media liver enzyme concentrations. Liver slices were treated with soluble egg antigen from Schistosoma japonicum eggs and cultured for 48hrs. Transcriptional changes were then analysed by microarray. The gene expression profile of the naive mouse liver slices cultered with and without the additional of soluble egg antigen (SEA) from Schistosoma japonicum eggs. Microarray analysis was performed on cRNA synthesised from total RNA. The liver of female 6 week old C57BL/6 mice were removed and then sectioned at 250um thickness using a vibrotome. Sections were cultered at 37oC and 5%CO2 in in William’s Medium E containing 25 mM glucose, 10 mg/ml gentamycin and 10% FBS. SEA was added at 10ug/ml and sections sampled at timepoints 0, 4hr, 24hr and 48hrs. Illumina mouse ref8_V2 arrays were used and fold changes compared to whole intact, precut tissue.
2014-12-12 | E-GEOD-64071 | biostudies-arrayexpress
Project description:We have performed a genome wide transcriptional survey of liver biopsies obtained from patients in Hunan China, who have chronic schistosomiasis with and without past viral hepatitis history, compared to patients with no liver disease history or indicators. These results present a comprehensive transcriptional profile of chronic schistosomiasis japonica patients and demonstrate similarities and differences with other hepatic diseases. These unique features of gene expression, in conjunction with previous reports of the cellular composition of granuloma formation and recovery, present an improved understanding of the molecular immunopathology and general physiological status underlying hepatic schistosomiasis.
2014-09-13 | GSE61376 | GEO
Project description:We have performed a genome wide transcriptional survey of liver biopsies obtained from patients in Hunan China, who have chronic schistosomiasis with and without past viral hepatitis history, compared to patients with no liver disease history or indicators. These results present a comprehensive transcriptional profile of chronic schistosomiasis japonica patients and demonstrate similarities and differences with other hepatic diseases. These unique features of gene expression, in conjunction with previous reports of the cellular composition of granuloma formation and recovery, present an improved understanding of the molecular immunopathology and general physiological status underlying hepatic schistosomiasis. The gene expression profile of the human liver was examined for chronic patients with Schistosoma japonicum infections. Microarray analysis was performed on cRNA synthesised from total RNA derived from the liver biopsy tissue from huan China. Three groups were examined based on infections status [C] were without history or indicators of schistosomiasis or viral heapatitis controls ; [S] with a history or active for schistosomiasis but no indicators of viral heapatitis; and [S]
2014-09-13 | E-GEOD-61376 | biostudies-arrayexpress
Project description:Maternal Schistosomiasis CD45+
| PRJNA680505 | ENA
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.
2014-08-31 | GSE59276 | GEO
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.
2014-08-31 | E-GEOD-59276 | biostudies-arrayexpress
Project description:Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel is still the only drug used for schistosomiasis treatment and reduction in drug efficiency has prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within S. mansoni gut is a major heme detoxification route involving lipid droplets in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of the antimalarial quinine (QN) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN (75mg/kg/day) from 11th to 17th day after infection decreased not only total, males and females worm burden (46.2 %-51.0 %), eggs production, but also the granulomatous reaction to parasite eggs trapped in the liver. These effects correlated with a significant impairment of Hz production (40%) specifically in S. mansoni females, being parallel to remarkable ultrastructural changes in female worms, particularly in the gut epithelium. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by QN treatment indicates that interference of Hz formation in S. mansoni is a valid chemotherapeutical target for development of new antischistosomal drugs.
2009-07-13 | GSE14751 | GEO
Project description:Background: Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population, and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity. Methodology: A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers. Results: A total of 1306 proteins and 8752 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70). Conclusion: These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis.
2017-10-24 | PXD006438 | Pride
Project description:Transcriptomics of the immune response to Schistosomiasis
| PRJEB2931 | ENA
Project description:Background: Although a number of intestinal inflammatory conditions pertain to the ileum, whole-genome gene expression analyses on ileal inflammation in animal models are lacking to date. Therefore, we aimed to identify and characterize alterations in gene expression in the acutely inflamed ileum of two murine models of intestinal inflammation, namely intestinal schistosomiasis and TNBS-induced ileitis, using Agilent whole-genome microarrays followed by bioinformatics analysis to detect enrichment of Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology categories. Results: When compared with healthy control mice, of almost all known mouse genes and transcripts represented on the array, intestinal schistosomiasis and TNBS-induced ileitis yielded 207 and 1417 differential genes respectively, with 48 overlapping genes (adj.p.value<0.1 and log2FC>1 or <1). Complement and coagulation cascades, extracellular matrix-receptor interaction, Fc epsilon receptor I signaling pathways and protein activation cascade, cell adhesion categories were enriched for differential genes in intestinal schistosomiasis. Antigen processing and presentation, cell adhesion molecules, ABC transporters, Toll-like receptor signaling pathways and response to chemical stimulus categories were enriched for differential genes in TNBS-induced ileitis. Although cytokine-cytokine receptor interaction, intestinal immune network for immunoglobulin A production, focal adhesion pathways and immune, inflammatory and defense response categories were enriched for differential genes in both inflammation models, the vast majority of the associated differential genes were unique to each model. Conclusions: This study characterized the two diverse models of ileal inflammation at a whole-genome level and outlined their underlying molecular heterogeneity. The results indicate that intestinal schistosomiasis involves Th2 responses, enhanced tissue repair and complement activation, while TNBS-induced ileitis involves Th17 responses, defective antigen processing and presentation and altered Toll-like receptor-mediated responses. Epithelial barrier impairment seems to occur in both inflammation models. Moreover, the comprehensive differential gene-list provided by this study would be helpful as a starting point to explore a specific novel pathway in more detail dealing with small bowel inflammation.
2012-10-05 | GSE31265 | GEO