С. А. Корниенко А. В. Кривопалов
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- MOLECULAR MECHANISMS OF BILIARY NEOPLASIA FORMATION IN OPISTHORCHIASIS: GLOBAL CHANGES IN GENE EXPRESSION Pakharukova M.Y., Zaparina O., Baginskaya N.V., Mordvinov V.A.
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Беэр С.А. 2005. Биология возбудителя описторхоза. Москва, Товарищество научных изданий КМК. 336 с. Gouveia M.J., Pakharukova M.Y., Laha T., Sripa B., Maksimova G.A., Rinaldi G., Brindley P.J., Mordvinov V.A., Amaro T., Santos L.L., Correia da Costa J.M., Vale N. 2017. Infection with Opisthorchis felineus induces intraepithelial neoplasia of the biliary tract in a rodent model. Carcinogenesis. 38(9):929–937. doi:10.1093/carcin/bgx042. Maksimova G.A., Pakharukova M.Y., Kashina E.V., Zhukova N.A., Kovner A.V., Lvova M.N., Katokhin A.V., Tolstikova T.G., Sripa B., Mordvinov V.A. 2017. Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters. Parasitol Int. 66, 458-463. doi:10.1016/j.parint.2015.10.002. Pakharukova M.Y., Correia da Costa J.M., Mordvinov V.A. 2019a. The liver fluke Opisthorchis felineus as a group III or group I Carcinogen. 4open, 2, 23. Pakharukova M.Y., Zaparina O.G., Kapushchak Y.K., Baginskaya N.V., Mordvinov V.A. 2019b. Opisthorchis felineus infection provokes timedependent accumulation of oxidative hepatobiliary lesions in the injured hamster liver. PLoS ONE, 14(5): e0216757. MOLECULAR MECHANISMS OF BILIARY NEOPLASIA FORMATION IN OPISTHORCHIASIS: GLOBAL CHANGES IN GENE EXPRESSION Pakharukova M.Y., Zaparina O., Baginskaya N.V., Mordvinov V.A. The causative agent of opisthorchiasis, the liver fluke Opisthorchis felineus (Rivolta, 1884), infests the bile ducts and the gallbladder of humans and fish-eating animals. This trematode is a representative of the triad of epidemiologically significant species of the Opisthorchiidae family (Beer, 2005). In humans, the disease has long duration and may contribute to the occurrence of precancerous changes in the liver, such as bile duct epithelial neoplasia (Gouveia et al., 2017; Maksimova et al., 2017; Pakharukova et al., 2019b), which under certain conditions can lead to Материалы VI межрегиональной научной конференции, 4–6 сентября 2019 117 primary liver cancer (Pakharukova et al., 2019a). Despite the obvious relevance of the study of opisthorchiasis, the molecular mechanisms of the occurrence of neoplastic processes in the liver during opisthorchiasis and the role of the liver fluke as a biological carcinogen remain unexplored. The aim of the work was to study the molecular mechanisms of neoplasia of the bile duct epithelium on an experimental model of opisthorchiasis, the golden hamster Mesocricetus auratus. The paper presents the first data on global changes in the host gene expression associated with liver fluke infection. In particular, an analysis of differential gene expression was carried out on the basis of the obtained data of genome-wide sequencing of liver transcriptomes (Illumina HiSeq2500) of hamsters infected with O. felineus 1- and 3-months post infection. The functional annotation of differentially expressed genes was performed by analyzing the representation of functional groups (Gene Set Enrichment Analysis). The gene list was annotated using the gene ontology dictionaries “Biological process” and «Molecular function». In order to conduct an in-depth study and obtain additional insights into the mechanisms by which O. felineus infection causes precancerous lesions of the liver, profiles of markers of chronic inflammation and fibrogenesis in the dynamics of opisthorchiasis (from 1 to 18 months after infection) were investigated using Western blot and Real-time PCR. Using immunohistochemistry, resident macrophages with various immunophenotypes in the liver has been demonstrated. It was also demonstrated, that the manifestation of oxidative stress (products of lipid peroxidation and oxidative DNA damage) was directly associated with the time of the infection and with the level of manifestation of neoplastic processes in the epithelium of the bile ducts. Thus, our data provide first insights into the global changes in the expression of host liver genes in animals infected with the liver fluke. We provide first data on the genes involved in various cellular pathways and biological processes associated with the pathogenesis and involved in the formation of biliary neoplasia in opisthorchiasis. жүктеу/скачать 7.14 Mb. Достарыңызбен бөлісу:
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