Microarray-based Gene Expression Profile In Balb/c Mouse Liver Infected With Echinococcos Multiltilocularis

Background and Objective Alveolar echinococcosis (AE) of the liver is a rare parasitic disease due to the intra-hepatic development of Echinococcus multilocularis (Em) larvae. It behaves like a slow-growing liver cancer and is characterized by a granulomatous host reaction that includes infiltration by cells involved in the immune response and fibrogenesis. Generally, AE has a long asymptomatic period (e.g., 5–20 years) followed by a rapid deterioration in health, and the untreated AE may result in a >90% fatal outcomes.Currently,liver transplant or partial hepatectomy combining with medical therapy is the only way to sustain patient'liver,and this method not bring only great pain to the patient,but also heavily economic burden.Although the immunology of Hydatid Disease has developed, the full repertoire of host genes whose expression is modulated by Echinococcus multilocularis as well as the signal transduction cascades underlying these changes are still unknown. In this study, we use cDNA microarray to characterize a mRNA expression profile of the liver in BALB/c mouse infected with Echinococcus multilocularis. Methods 45 BALB/c mice were randomly divided into two groups: experimental group (30 mice) and control group (15 mice). Em infection was performed after laparotomy by intra-hepatic injection of the metacestode suspension (experimental animals) or of the medium used to prepare the metacestode suspension (control animals) under a surgery microscope method.8 weeks,12weeks and 24weeks after infection, the mouse liver samples were collected and used to extract total RNA respectively. 10 mice for each time point from experimental group and 5 mice from control group were prepared. The expression levels of approximately 25,000 genes were analyzed in the BALB/c mouse liver infected with Echinococcus multilocularis compared with the liver from control group by cDNA microarray. Molecular Annotation System 2.0 was used to analyze the biological functions of significantly altered genes. The microarray data validation was confirmed by quantitative real-time reverse transcription PCR(qRT-PCR).Results The microarray showed that eight weeks after infection the expression levels of 108 genes were remarkably altered, 75 of the genes were up-regulated and 33 genes were down-regulated. Twelve weeks after infection, 139 genes were significantly altered, 111 up-regulated and 28 down-regulated. Twenty four weeks after infection, 279 genes were significantly altered, 144 up-regulated and 135 down-regulated. There are 61 dramatically altered genes occurred at least at two time points. Those altered genes were mainly associated with metabolism, transport, apoptosis, cell cycle, response to stimulus, immune response, signal transduction etc. In some functional categories, such as metabolism and transport, more and more genes occurred with time went by. Conclusions Many differentially expressed genes with different functions interact with each other to result in liver injury by Echinococcus multilocularis infection. Gene Pparα(peroxisome proliferator activated peceptor alpha),Growth Arrest and DNA Damage-45 (GADD45) family,Heat Shock Protein family,serine peptidase inhibitor And MAPK signal pathway might take part in the liver injury caused by the infecion of Echinococcus multilocularis and play an important role during the process. Discovering and studying such candidate genes of protective effects may be of help to prevent Echinococcus multilocularis infectious liver injury and to treat this serious disorder.