Suppression of Ov-grn-1 encoding granulin of Opisthorchis viverrini inhibits proliferation of biliary epithelial cells

Papatpremsiri, Atiroch; Smout, Michael J.; Loukas, Alex; Brindley, Paul J.; Sripa, Banchob; Laha, Thewarach

doi:10.1016/j.exppara.2014.11.004

Cited by 29 publications

(46 citation statements)

References 46 publications

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“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 18 The non-malignant cholangiocyte cell line H69 is a SV40-transformed human bile duct epithelial cell line derived from human liver, kindly provided by Dr. Gregory J. Gores, Mayo Clinic, Rochester, Minnesota. H69 cells 23,29,30 were maintained in T75cm 2 vented flasks (Corning) as monolayers as described 31 …”

Section: Nmr Spectroscopy and Structure Determinationmentioning

confidence: 99%

Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold

et al. 2017

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Granulins are a family of protein growth factors that are involved in cell proliferation. An orthologue of granulin from the human parasitic liver fluke Opisthorchis viverrini, known as Ov-GRN-1, induces angiogenesis and accelerates wound repair. Recombinant Ov-GRN-1 production is complex and poses an obstacle for clinical development. To identify the bioactive region(s) of Ov-GRN-1, four truncated N-terminal analogues were synthesized and characterized structurally using NMR spectroscopy. Peptides that contained only two native disulfide bonds lack the characteristic granulin β-hairpin structure. Remarkably, the introduction of a non-native disulfide bond was critical for formation of β-hairpin structure. Despite this structural difference, both two and three disulfide-bonded peptides drove proliferation of a human cholangiocyte cell line and demonstrated potent wound healing in mice. Peptides derived from Ov-GRN-1 are leads for novel wound healing therapeutics, as they are likely less immunogenic than the full-length protein and more convenient to produce.

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Section: Nmr Spectroscopy and Structure Determinationmentioning

confidence: 99%

Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold

et al. 2017

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“…These similarities led us to hypothesize that the effects of BgGRN on the capacity of snails to fight of S. mansoni infections might be conserved across various strains of B. glabrata and various Biomphalaria species due to their evolutionary relatedness. We also had reason to believe that the recombinant granulin we generated from B. glabrata would retain its functionality across Biomphalaria species due to the fact that granulin from Opisthorchis viverrini is capable of inducing cell proliferation in humans, despite the distance between these two species [34,35].…”

Section: Discussionmentioning

confidence: 99%

Biomphalaria glabrata Granulin Increases Resistance to Schistosoma mansoni Infection in Several Biomphalaria Species and Induces the Production of Reactive Oxygen Species by Haemocytes

Hambrook

Gharamah

Pila

et al. 2019

Genes

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Gastropod molluscs, which have co-evolved with parasitic digenean trematodes for millions of years, utilize circulating heamocytes as the primary method of containing and killing these invading parasites. In order to do so, they must generate suitable amounts of haemocytes that are properly armed to kill parasitic worms. One method by which they generate the haemocytes required to initiate the appropriate cell mediated immune response is via the production and post-translational processing of granulins. Granulins are an evolutionarily conserved family of growth factors present in the majority of eukaryotic life forms. In their pro-granulin form, they can elicit cellular replication and differentiation. The pro-granulins can be further processed by elastase to generate smaller granulin fragments that have been shown to functionally differ from the pro-granulin precursor. In this study, we demonstrate that in vivo addition of Biomphalaria glabrata pro-granulin (BgGRN) can reduce Schistosoma mansoni infection success in numerous Biomphalaria sp. when challenged with different S. mansoni strains. We also demonstrate that cleavage of BgGRN into individual granulin subunits by elastase results in the stimulation of haemocytes to produce reactive oxygen species.

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“…It is believed that liver flukes can cause damage to the bile duct epithelium in several ways: (i) via mechanical damage; (ii) as a result of action of reactive oxygen species that are produced by the host cells at the site of inflammation; and (iii) because of direct action of fluke-secreted proteins that induce cell proliferation and inhibit apoptosis [34–36]. All these processes lead to lesions in the genetic material and mutations, which get fixed after DNA replication.…”

Section: Discussionmentioning

confidence: 99%

Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters

Maksimova

Pakharukova

Кашина

et al. 2017

Parasitology International

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The food-borne liver trematode Opisthorchis felineus is an emerging source of biliary tract diseases on the territory of the former Soviet Union and Eastern Europe. This parasite along with trematodes Opisthorchis viverrini and Clonorchis sinensis belong to the triad of epidemiologically important liver flukes of the Opisthorchiidae family. It is known that O. viverrini and C. sinensis are the main risk factors of cholangiocarcinoma (CCA) in the endemic regions. The carcinogenic potential of O. felineus has not been well researched because of the absence of systematic pathomorphological, clinical, and epidemiological studies on O. felineus opisthorchiasis. In the present study, we show the results of detailed histopathological analysis and comprehensive evaluation of inflammation, bile duct dysplasia, periductal fibrosis, bile duct hyperplasia, bile duct proliferation, egg granuloma, cysts, cholangiofibrosis, and CCA from 10 to 30 weeks following infection of Syrian hamsters with O. felineus accompanied by oral administration of dimethylnitrosamine (DMN). The results revealed that O. felineus contributes to bile duct cancer development in the hamster model. During the combined action of O. felineus and DMN, morphological features of the liver underwent dramatic changes at the cellular and organ levels. Already in the early stages of the experiment, we observed extensive periductal fibrosis, active inflammation, proliferation of the bile duct, bile duct dysplasia and egg granulomas. Later, against the background of all these changes, cholangiofibrosis and CCA were found. Our work is the first step in the study of carcinogenic potential of O. felineus. Obtained data indicate the risk of CCA of patients having chronic O. felineus opisthorchiasis, and underscore the need for the development of programs for control of this helminthiasis.

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Suppression of Ov-grn-1 encoding granulin of Opisthorchis viverrini inhibits proliferation of biliary epithelial cells

Cited by 29 publications

References 46 publications

Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold

Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold

Biomphalaria glabrata Granulin Increases Resistance to Schistosoma mansoni Infection in Several Biomphalaria Species and Induces the Production of Reactive Oxygen Species by Haemocytes

Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters

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