Ekaterina Lishai (Novosibirsk / RU), Dr. Maria Pakharukova (Novosibirsk / RU), Oxana Zaparina (Novosibirsk / RU), Prof. Sung- Jong Hong (Incheon / KR), Prof. Banchob Sripa (Khon Kaen / TH), Dr. Viatcheslav Mordvinov (Novosibirsk / RU)
Abstract text
The foodborne trematodes Opisthorchis felineus, O. viverrini and Clonorchis sinensis induce liver fluke infections in mammals, including humans. The species have different carcinogenic potential: O. viverrini and C. sinensis are assigned to Group 1A of biological carcinogens, while O. felineus belongs to Group 3A.
To provide in-depth research and to gain insights into the species-specific mechanism by which liver fluke infections cause liver lesions we investigated differential gene expression of liver transcriptomes (Illumina HiSeq2500) of golden hamsters infected with O. felineus, O. viverrini and C. sinensis at 1 and 3 months postinfection.
The libraries contained 905,079,329 sequences (average 37,711,638.7 reads per sample). The STAR aligner, DESeq2, clusterProfiler and BisqueRNA R-packages were applied.
Principal components analysis revealed high clustering of samples by species and by the time in infection. In C. sinensis infection, the highest number (2886) differentially expressed genes (DEGs) were observed. Whereas O. felineus and O. viverrini infections change the expression of 1790 and 1501 DEGs, respectively.
Cluster analysis revealed that activated cellular pathways were different between acute and chronic infection. Transcriptomic data were supported by the results of western blotting, revealing the presence of fibrogenesis-related proteins. DEGs were enriched by common MSigDB signatures such as myogenesis, inflammatory response, late estrogen response, IL2 STAT5 signaling, TNFA signaling via NFKB for all three infections. Epithelial-to-mesenchymal transition, IL6 JAK STAT3 signaling, and TGFB signaling were represented in C. sinensis and O. felineus- infected hamster, but not after O. viverrini infection.
Common enriched KEGG pathways were Hippo, PI3K-Akt and calcium signaling pathways, while PPAR signaling pathway was present only in C. sinensis and O. viverrini infections. Significant interspecies differences in the response of cholangiocytes, stellate cells and M1 macrophages were found.
Our data provide knowledge about species-specific changes in gene expression in the liver fluke–infected host liver and contribute to understanding the biliary fibrosis and neoplasia associated with liver fluke infections. This work was supported by the Russian Science Foundation [grant number 22-24-20010].