Global changes in gene expression related to Opisthorchis felineus liver fluke infection reveal temporal heterogeneity of a mammalian host response

IF 2.9 Q2 PARASITOLOGY

Food and Waterborne Parasitology Pub Date : 2022-06-01 DOI:10.1016/j.fawpar.2022.e00159

Maria Y. Pakharukova , Oxana Zaparina , Nina V. Baginskaya , Viatcheslav A. Mordvinov

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引用次数: 6

Abstract

The food-borne trematode Opisthorchis felineus colonizes bile ducts of the liver of fish-eating mammals including humans. Among chronically infected individuals, this opisthorchiasis involves hepatobiliary problems, including chronic inflammation, periductal fibrosis, biliary intraepithelial neoplasia, and even cholangiocarcinoma. Despite numerous studies at the pathomorphological level, the systemic response and cellular pathogenesis of these disorders are not well studied.

To conduct in-depth research and to gain insights into the mechanism by which O. felineus infection causes precancerous liver lesions, we (i) applied a next-generation-sequencing–based technology (high-throughput mRNA sequencing) to identify differentially expressed genes in the liver of golden hamsters infected with O. felineus at 1 and 3 months postinfection and (ii) verified the most pronounced changes in gene expression by western blotting and immunohistochemistry.

A total of 2151 genes were found to be differentially expressed between uninfected and infected hamsters (“infection” factor), whereas 371 genes were differentially expressed when we analyzed “time × infection” interaction. Cluster analysis revealed that sets of activated genes of cellular pathways were different between acute (1 month postinfection) and chronic (3 months postinfection) opisthorchiasis. This enriched KEGG pathways were “Cell adhesion molecules”, “Hippo signaling”, “ECM-receptor interaction”, “Cell cycle”, “TGF-beta”, and “P53 signaling”. Moreover, epithelial–mesenchymal transition was the most enriched (q-value = 2.2E-07) MSigDB hallmark in the set of differentially expressed genes of all O. felineus–infected animals. Transcriptomic data were supported by the results of western blotting and immunohistochemistry revealing the upregulation of vimentin, N-cadherin, and α-smooth muscle actin postinfection.

Our data expand knowledge about global changes in gene expression in the O. felineus–infected host liver and contribute to understanding the biliary neoplasia associated with the liver fluke infection.

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与猫腹蛇肝吸虫感染相关的基因表达的全球变化揭示了哺乳动物宿主反应的时间异质性

食鱼性吸虫寄生在包括人类在内的食鱼哺乳动物肝脏的胆管中。在慢性感染个体中，这种胆索病涉及肝胆问题，包括慢性炎症、管周纤维化、胆道上皮内瘤变，甚至胆管癌。尽管在病理形态学水平上进行了大量研究，但这些疾病的全身反应和细胞发病机制尚未得到很好的研究。为了深入研究狐猴感染导致癌前肝脏病变的机制，我们(i)应用基于下一代测序的技术(高通量mRNA测序)在感染狐猴后1个月和3个月鉴定了金仓鼠肝脏中差异表达的基因，(ii)通过western blotting和免疫组织化学验证了基因表达的最显著变化。共有2151个基因在未感染和感染仓鼠之间存在差异表达(“感染”因子)，而在分析“时间×感染”相互作用时，有371个基因存在差异表达。聚类分析显示急性(感染后1个月)和慢性(感染后3个月)蛇胸蚴病细胞通路的激活基因组不同。这些富集的KEGG通路分别是“细胞粘附分子”、“Hippo信号传导”、“ecm受体相互作用”、“细胞周期”、“tgf - β”和“P53信号传导”。此外，上皮-间质转化是所有感染猫伊蚊的动物差异表达基因中最丰富的(q值= 2.22 -07)MSigDB标志。western blotting和免疫组化结果支持转录组学数据，显示感染后vimentin、N-cadherin和α-平滑肌肌动蛋白上调。我们的数据扩展了对感染O. felineus宿主肝脏基因表达全局变化的认识，并有助于理解与肝吸虫感染相关的胆道肿瘤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Food and Waterborne Parasitology Immunology and Microbiology-Parasitology

CiteScore

5.10

自引率

4.00%

发文量

审稿时长

13 weeks

期刊介绍： Food and Waterborne Parasitology publishes high quality papers containing original research findings, investigative reports, and scientific proceedings on parasites which are transmitted to humans via the consumption of food or water. The relevant parasites include protozoa, nematodes, cestodes and trematodes which are transmitted by food or water and capable of infecting humans. Pertinent food includes products of animal or plant origin which are domestic or wild, and consumed by humans. Animals and plants from both terrestrial and aquatic sources are included, as well as studies related to potable and other types of water which serve to harbor, perpetuate or disseminate food and waterborne parasites. Studies dealing with prevalence, transmission, epidemiology, risk assessment and mitigation, including control measures and test methodologies for parasites in food and water are of particular interest. Evidence of the emergence of such parasites and interactions among domestic animals, wildlife and humans are of interest. The impact of parasites on the health and welfare of humans is viewed as very important and within scope of the journal. Manuscripts with scientifically generated information on associations between food and waterborne parasitic diseases and lifestyle, culture and economies are also welcome. Studies involving animal experiments must meet the International Guiding Principles for Biomedical Research Involving Animals as issued by the Council for International Organizations of Medical Sciences.