Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis
نویسندگان
چکیده
Toxic liver injury causes necrosis and fibrosis, which may lead to cirrhosis and liver failure. Despite recent progress in understanding the mechanism of liver fibrosis, our knowledge of the molecular-level details of this disease is still incomplete. The elucidation of networks and pathways associated with liver fibrosis can provide insight into the underlying molecular mechanisms of the disease, as well as identify potential diagnostic or prognostic biomarkers. Towards this end, we analyzed rat gene expression data from a range of chemical exposures that produced observable periportal liver fibrosis as documented in DrugMatrix, a publicly available toxicogenomics database. We identified genes relevant to liver fibrosis using standard differential expression and co-expression analyses, and then used these genes in pathway enrichment and protein-protein interaction (PPI) network analyses. We identified a PPI network module associated with liver fibrosis that includes known liver fibrosis-relevant genes, such as tissue inhibitor of metalloproteinase-1, galectin-3, connective tissue growth factor, and lipocalin-2. We also identified several new genes, such as perilipin-3, legumain, and myocilin, which were associated with liver fibrosis. We further analyzed the expression pattern of the genes in the PPI network module across a wide range of 640 chemical exposure conditions in DrugMatrix and identified early indications of liver fibrosis for carbon tetrachloride and lipopolysaccharide exposures. Although it is well known that carbon tetrachloride and lipopolysaccharide can cause liver fibrosis, our network analysis was able to link these compounds to potential fibrotic damage before histopathological changes associated with liver fibrosis appeared. These results demonstrated that our approach is capable of identifying early-stage indicators of liver fibrosis and underscore its potential to aid in predictive toxicity, biomarker identification, and to generally identify disease-relevant pathways.
منابع مشابه
Therapeutic Potential of Mouse Bone Marrow Mesenchymal Stem Cells in Carbon Tetrachloride (Ccl4)-Induced Liver Fibrosis
Purpose: To study the effect of allogenic bone marrow mesenchymal stem cells (BMMSCs) transplantation on carbon tetrachloride-induced liver fibrosis in mice. Materials and Methods: Fifty five female NMRI mice were divided in 5 groups, and to induce liver fibrosis CCL4 intraperitonealy was injected 1ml/Kg twice a week for 8 weeks 106 allogenic BMMSCs were infused in cell therapy group via tail v...
متن کاملThe Effect of Fatty Liver Disease on the Expression of RXFP1 and CTGF Genes in Cardiac Tissue of Wistar Rats
Background & Aims: Performing physical activity and having a healthy body is one of the most essential life needs of people with fatty liver. In recent years, studies have been performed on the relationship between fatty liver and arthrosclerosis. The results of these studies indicate the relationship between the Non-alcoholic fatty liver and arthrosclerosis of coronary artery disease. Non-alco...
متن کاملIdentification and prioritization genes related to Hypercholesterolemia QTLs using gene ontology and protein interaction networks
Gene identification represents the first step to a better understanding of the physiological role of the underlying protein and disease pathways, which in turn serves as a starting point for developing therapeutic interventions. Familial hypercholesterolemia is a hereditary metabolic disorder characterized by high low-density lipoprotein cholesterol levels. Hypercholesterolemia is a quantitativ...
متن کاملAssessment of hepatic fibrosis by transient elastography in rheumatoid arthritis patients receiving methotrexate
Background and Aim: Methotrexate (MTX) is commonly used in the treatment of diseases such as rheumatoid arthritis (RA) but, its hepatotoxicity potential, always has been a major concern. The aim of this study is to determine the rate of liver fibrosis by transient elastography (TE) method and its relationship with cumulative dose of MTX and duration of treatment, in rheumatoid arthritis patient...
متن کاملModulation of IKKβ/NF-κB and TGF-β1/Smad via Fuzheng Huayu recipe involves in prevention of nutritional steatohepatitis and fibrosis in mice
Objective(s):Fuzheng Huayu recipe (FZHY) exerts significant protective effects against liver fibrosis by strengthening the body’s resistance and removing blood stasis. However, the molecular mechanisms through which FZHY affects liver fibrosis are still unclear. In this study, we examined the expression levels of factors involved in the inhibitor κB kinase-β (IKK-β)/nuclear factor-κB (NF-κB) an...
متن کامل