Granulin Expression in Hamsters during Opisthorchis viverrini Infection-Induced Cholangiocarcinogenesis 2018

Songkiad Upontain, and Piya Sereerak, and Thewarach Laha, and Banchob Sripa, and Prasarn Tangkawatana, and Paul J Brindley, and Sirikachorn Tangkawatana
Graduate School, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand.

The secreted growth factor granulin (GRN) is upregulated during diverse epithelial cancers. GRN stimulates cell growth and development while inhibiting apoptosis. Orthologues of vertebrate granulins evolved in other animals including the liver fluke Opisthorchis viverrini. Curiously, liver fluke granulin, termed Ov-GRN-1 promotes cholangiocarcinogenesis during chronic opisthorchiasis but, by contrast, limited information is available concerning mammalian GRN during liver fluke infection-induced cholangiocarcinoma (CCA). Here we investigated the expression of mammalian granulin in the O. viverrini-associated a hamster model of opisthorchiasis and liver fluke infection-induced CCA. Male Syrian golden hamsters were assigned to one of four treatment groups, each group included 30 hamsters: 1) normal (control), 2) infected with O. viverrini (OV); 3) exposed to N-dimethylnitrosamine in drinking water (DMN); and 4) infected with O. viverrini and exposed to DMN (OVDMN). Immunohistochemistry using an anti-granulin specific probe for mammalian granulin was undertaken to monitor expression and location in hepatobiliary tissues of the hamsters. In parallel, cognate studies of transcription of mRNA and protein. Histopathological examination revealed development of proliferative lesions from the onset and eruption of CCA onwards, an outcome that was most prominent in the OVDMN hamsters. Proliferating cell nuclear antigen (PCNA) index rose continuously from initiation of infection and increased with lesion progression in OV, DMN and markedly in OVDMN hamsters. Expression of GRN in biliary was elevated in biliary epithelial cells in CCA lesions in hamsters in the DMN and OVDMN groups. Expression of GRN as assayed by western blot and RT-PCR reflected the same trend as seen with PCNA. Together the histopathogical and molecular assay based findings revealed marked expression of granulin during cholangiocarcinoma in these hamsters, and highlighted the prospect that granulin represents a potential prognostic marker for cholangiocarcinoma.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008297 Male Males
D009889 Opisthorchiasis Infection with flukes of the genus Opisthorchis. Opisthorchis Infection,Opisthorchis felineus Infection,Opisthorchis viverrini Infection,Infection, Opisthorchis,Infection, Opisthorchis felineus,Infection, Opisthorchis viverrini,Infections, Opisthorchis,Infections, Opisthorchis felineus,Infections, Opisthorchis viverrini,Opisthorchiases,Opisthorchis Infections,Opisthorchis felineus Infections,Opisthorchis viverrini Infections
D009891 Opisthorchis A genus of trematode liver flukes of the family Opisthorchidae. It consists of the following species: O. felineus, O. noverca (Amphimerus noverca), and O. viverrini. The intermediate hosts are snails, fish, and AMPHIBIANS. Opisthorchis felineus,Opisthorchis viverrini,Opisthorchi,Opisthorchis viverrinus,viverrini, Opisthorchis
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005210 Fasciola hepatica A species of helminth commonly called the sheep liver fluke. It occurs in the biliary passages, liver, and gallbladder during various stages of development. Snails and aquatic vegetation are the intermediate hosts. Occasionally seen in man, it is most common in sheep and cattle. Liver Fluke,Fasciola hepaticas,Fluke, Liver,Flukes, Liver,Liver Flukes,hepatica, Fasciola
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000077155 Granulins Small, cysteine-rich peptides generated by the proteolytic cleavage of progranulin. Granulin peptides are each composed of a granulin-motif, while paragranulin is composed of a half-granulin motif. The mammalian granulins are named granulin 1-7 for their sequence order in the progranulin propeptide, and are alternately named granulin G, F, B, A, C, D, and E; or epithelin 7, 6, 2, 1, 3, 4, and 5, i.e. granulin 1 aka granulin G aka epithelin 7, etc. Epithelin,Granulin,Epithelin 1,Epithelin 2,Epithelin 3,Epithelin 4,Epithelin 5,Epithelin-1,Epithelin-2,Epithelin2,Epithelins,Granulin (123-179),Granulin (206-261),Granulin 1,Granulin 2,Granulin 3,Granulin 4,Granulin 5,Granulin 6,Granulin 7,Granulin A,Granulin B,Granulin C,Granulin D,Granulin E,Granulin F,Granulin G,Granulin Peptide (281-336),Granulin Peptide (58 -113),Granulin Peptides,Granulin-3,Granulin3,Paragranulin,5, Granulin

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