Omics-based investigation of pathological liver injury induced by Echinococcus multilocularis infection in mice.

Alveolar echinococcosis (AE) can cause severe liver injury and be fatal if left untreated. Currently, there are no effective therapeutic options for AE-induced liver injury. Therefore, by exploring the changes of gene proteins in mice with damaged liver, we attempted to identify the key molecules of liver damage, and provide data that will enable the development of drugs targeting hepatic AE. BALB/c mice were inoculated with protoscoleces via the hepatic portal vein. Three months later, B-ultrasound examination and Hematoxylin—eosin (H&E) staining were used to confirm liver damage in mice. RNA sequencing and Liquid chromatography–mass spectrometry (LC-MS) were used to screen differentially expressed molecules associated with liver damage through bioinformatics, and Quantitative Real-Time PCR (qRT-PCR) was used to verify their expression. B-ultrasound examination showed liver lesions in the infected group, and H&E staining showed liver inflammation, fibrosis and liver necrosis. RNA sequencing and LC-MS results showed changes in the levels of more than 1000 genes and proteins, with upregulation of immune and inflammation pathways. By contrast, the downregulated genes and proteins were mostly involved in various metabolic reactions. Correlation analysis was conducted between the transcriptome data and proteome data. The results revealed 240 differentially expressed genes, of which 192 were upregulated, and 48 were downregulated. Many of these genes were involved in metabolic reactions, such as Catalase (Cat), fatty acid synthase (Fasn), and IL-16 genes, which may have relevance to liver injury. The results of qRT-PCR were consistent with those of bioinformatics analysis. The mechanisms of liver injury in mice infected with Echinococcus multilocularis are complex, involving abnormal metabolism, oxidative stress, inflammatory response, and many other factors. This study provides the data for preliminary exploration for the development of targeted therapies against AE. Alveolar echinococcosis is a zoonotic parasitic disease that causes cysts to form in a number of organs of the body, but primarily in the liver. It can be a life-threatening infection. In this study, transcriptome sequencing and proteomic mass spectrometry were used to analyze the complex mechanisms of liver damage in mice infected with this parasite, and bioinformatics methods were used to correlate the resulting data to study the liver damage at the genetic level. We found that the liver injury mechanism of multilocular Echinococcus multilocularis -infected mice is very complex, involving metabolic abnormalities, oxidative stress, inflammation, and other factors. According to the transcriptome and proteome and the results of association analysis, immunity and metabolism play a major role. Finally, liver injury genes such as Cat, Fasn, and IL-16 were screened out. The exploration and analysis data of these genes could assist in the study of the pathogenesis of AE and the development of targeted therapeutic drugs. [Display omitted] [ABSTRACT FROM AUTHOR]