ArticleExperimental parasitology2015
Suppression of Ov-grn-1 encoding granulin of Opisthorchis viverrini inhibits proliferation of biliary epithelial cells.
Article in Experimental parasitology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- From infection to cholangiocarcinoma: Why opisthorchiids break these rules.One health (Amsterdam, Netherlands) · 2026Review
- Fluke-borne viruses are a risk factor for diseases caused by carcinogenic trematodes.bioRxiv : the preprint server for biology · 2025Article
- Mechanistic insights into liver-fluke-induced bile-duct cancer.Trends in parasitology · 2024Review
- Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini.PLoS pathogens · 2022Article
- Review
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- Article
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- Structural Variants of a Liver Fluke Derived Granulin Peptide Potently Stimulate Wound Healing.Journal of medicinal chemistry · 2018Article
- Granulin Expression in Hamsters during Opisthorchis viverrini Infection-Induced CholangiocarcinogenesisAsian Pacific journal of cancer prevention : APJCP · 2018Article
- Liver Fluke-Associated Biliary Tract Cancer.Gut and liver · 2018Review
- Opisthorchis viverrini Proteome and Host-Parasite Interactions.Advances in parasitology · 2018Review
- Granulin Secreted by the Food-Borne Liver FlukeFrontiers in medicine · 2018Article
- Suppression of mRNAs encoding CD63 family tetraspanins from the carcinogenic liver fluke Opisthorchis viverrini results in distinct tegument phenotypes.Scientific reports · 2017Article
- Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters.Parasitology international · 2017Article
- Clonorchis sinensis granulin: identification, immunolocalization, and function in promoting the metastasis of cholangiocarcinoma and hepatocellular carcinoma.Parasites & vectors · 2017Article
- Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold.Journal of medicinal chemistry · 2017Article
- Liver fluke infection and cholangiocarcinoma: a review.Parasitology research · 2017Review
- Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia.PLoS pathogens · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Multistep processes likely underlie cholangiocarcinogenesis induced by chronic infection with the fish-borne liver fluke, Opisthorchis viverrini. One process appears to be cellular proliferation of the host bile duct epithelia driven by excretory-secretory (ES) products of this pathogen. Specifically, the secreted growth factor Ov-GRN-1, a liver fluke granulin, is a prominent component of ES and a known driver of hyper-proliferation of cultured human and mouse cells in vitro. We show potent hyper-proliferation of human cholangiocytes induced by low nanomolar levels of recombinant Ov-GRN-1 and similar growth produced by low microgram concentrations of ES products and soluble lysates of the adult worm. To further explore the influence of Ov-GRN-1 on the flukes and the host cells, expression of Ov-grn-1 was repressed using RNA interference. Expression of Ov-grn-1 was suppressed by 95% by day 3 and by ~100% by day 7. Co-culture of Ov-grn-1 suppressed flukes with human cholangiocyte (H-69) or human cholangiocarcinoma (KKU-M214) cell lines retarded cell hyper-proliferation by 25% and 92%, respectively. Intriguingly, flukes in which expression of Ov-grn-1 was repressed were less viable in culture, suggesting that Ov-GRN-1 is an essential growth factor for survival of the adult stage of O. viverrini, at least in vitro. To summarize, specific knock down of Ov-grn-1 reduced in vitro survival and capacity of ES products to drive host cell proliferation. These findings may help to contribute to a deeper understanding of liver fluke induced cholangiocarcinogenesis.
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