Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial Cells
The liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the O. viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caus...
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Frontiers Media S.A.
2018-02-01
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmed.2018.00030/full |
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| author | Brandon Haugen Brandon Haugen Shannon E. Karinshak Victoria H. Mann Anastas Popratiloff Alex Loukas Paul J. Brindley Michael J. Smout |
| author_facet | Brandon Haugen Brandon Haugen Shannon E. Karinshak Victoria H. Mann Anastas Popratiloff Alex Loukas Paul J. Brindley Michael J. Smout |
| author_sort | Brandon Haugen |
| collection | DOAJ |
| description | The liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the O. viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the liver fluke represent wounds that undergo protracted cycles of healing and re-injury during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile duct cancer, cholangiocarcinoma. An ES protein, the secreted granulin-like growth factor termed Ov-GRN-1, accelerates wound resolution in mice and in vitro. To investigate angiogenesis (blood vessel development) that may contribute to wound healing promoted by liver fluke granulin and, by implication, to carcinogenesis during chronic opisthorchiasis, we employed an in vitro tubule formation assay (TFA) where human umbilical vein endothelial cells were grown on gelled basement matrix. Ten and 40 nM Ov-GRN-1 significantly stimulated angiogenesis as monitored by cellular proliferation and by TFA in real time. This demonstration of potent angiogenic property of Ov-GRN-1 bolsters earlier reports on the therapeutic potential for chronic non-healing wounds of diabetics, tobacco users, and the elderly and, in addition, showcases another of the hallmark of cancer characteristic of this carcinogenic liver fluke. |
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| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-12T02:03:02Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-a9b28bbc4aa445a1aa2e442a34ea66e42022-12-22T00:42:07ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2018-02-01510.3389/fmed.2018.00030332508Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial CellsBrandon Haugen0Brandon Haugen1Shannon E. Karinshak2Victoria H. Mann3Anastas Popratiloff4Alex Loukas5Paul J. Brindley6Michael J. Smout7Department of Microbiology, Immunology and Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, United StatesDepartment of Biology, University of the District of Columbia, Washington, DC, United StatesDepartment of Microbiology, Immunology and Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, United StatesDepartment of Microbiology, Immunology and Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, United StatesNanofabrication and Imaging Center, Office of VP for Research, George Washington University, Washington, DC, United StatesCentre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, AustraliaDepartment of Microbiology, Immunology and Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, United StatesCentre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, AustraliaThe liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the O. viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the liver fluke represent wounds that undergo protracted cycles of healing and re-injury during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile duct cancer, cholangiocarcinoma. An ES protein, the secreted granulin-like growth factor termed Ov-GRN-1, accelerates wound resolution in mice and in vitro. To investigate angiogenesis (blood vessel development) that may contribute to wound healing promoted by liver fluke granulin and, by implication, to carcinogenesis during chronic opisthorchiasis, we employed an in vitro tubule formation assay (TFA) where human umbilical vein endothelial cells were grown on gelled basement matrix. Ten and 40 nM Ov-GRN-1 significantly stimulated angiogenesis as monitored by cellular proliferation and by TFA in real time. This demonstration of potent angiogenic property of Ov-GRN-1 bolsters earlier reports on the therapeutic potential for chronic non-healing wounds of diabetics, tobacco users, and the elderly and, in addition, showcases another of the hallmark of cancer characteristic of this carcinogenic liver fluke.http://journal.frontiersin.org/article/10.3389/fmed.2018.00030/fullgranulinparasiteangiogenesiswound healingliver cancerhuman umbilical vein endothelial cells |
| spellingShingle | Brandon Haugen Brandon Haugen Shannon E. Karinshak Victoria H. Mann Anastas Popratiloff Alex Loukas Paul J. Brindley Michael J. Smout Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial Cells Frontiers in Medicine granulin parasite angiogenesis wound healing liver cancer human umbilical vein endothelial cells |
| title | Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial Cells |
| title_full | Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial Cells |
| title_fullStr | Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial Cells |
| title_full_unstemmed | Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial Cells |
| title_short | Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial Cells |
| title_sort | granulin secreted by the food borne liver fluke opisthorchis viverrini promotes angiogenesis in human endothelial cells |
| topic | granulin parasite angiogenesis wound healing liver cancer human umbilical vein endothelial cells |
| url | http://journal.frontiersin.org/article/10.3389/fmed.2018.00030/full |
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