| Involvement of MMP-9 in peribiliary fibrosis and cholangiocarcinogenesis via Rac1-dependent DNA damage in a hamster model. | |
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MedLine Citation:
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PMID: 20162672 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Peribiliary fibrosis caused by chronic infection with Opisthorchis viverrini (OV) is a risk factor of cholangiocarcinoma (CCA) in northeastern Thailand. Matrix metalloproteinases (MMPs) are enzymes capable of degrading and remodeling the extracellular matrix in the process of fibrosis and carcinogenesis. We examined MMPs expression and their role in fibrogenesis and cholangiocarcinogenesis in hamsters treated with OV and N-nitrosodimethylamine (NDMA). We assessed the time profiles of MMPs, inducible nitric oxide synthase (iNOS), Rac1, α-smooth muscle actin (α-SMA) and DNA lesions (8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG) in relation to fibrosis and CCA development. Histopathology revealed OV and NDMA synergistically induced peribiliary fibrosis time-dependently, and CCA occurred at 3 months, whereas OV or NDMA alone induced less fibrosis. Hydroxyproline levels in the liver and plasma were positively associated with the expression of collagen I and α-SMA. MMP-9 expression was significantly increased and correlated with the accumulation of myofibroblast, fibrosis levels and cholangiocarcinogenesis. MMP-9 activity was correlated with iNOS, and immunocolocalization was observed in inflammed tissues, early and invasive CCA. OV and NDMA synergistically induced MMP-9 expression in association to Rac1. In addition, Rac1 was colocalized with iNOS, and 8-nitroguanine, in inflammed tissues and CCA. Formation of 8-nitroguanine and 8-oxodG increased with tumor progression. The results suggest that MMP-9 expression is associated with the accumulation of peribiliary fibrosis in conjunction to the induction of iNOS and Rac1 that may potentiate DNA damage and cholangiocarcinogenesis. |
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Authors:
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Suksanti Prakobwong; Puangrat Yongvanit; Yusuke Hiraku; Chawalit Pairojkul; Paiboon Sithithaworn; Porntip Pinlaor; Somchai Pinlaor |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 127 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-09-29 Completed Date: 2010-11-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 2576-87 Citation Subset: IM |
Affiliation:
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Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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biosynthesis Animals Bile Duct Diseases / genetics, metabolism*, pathology Bile Ducts / pathology Cell Transformation, Neoplastic / genetics, metabolism*, pathology Cholangiocarcinoma / genetics, metabolism*, parasitology, pathology Collagen / biosynthesis, genetics, metabolism Cricetinae DNA Damage* Disease Models, Animal Fibrosis Liver / metabolism Male Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / biosynthesis, metabolism* Mesocricetus Nitric Oxide Synthase Type II / biosynthesis Opisthorchiasis / genetics, metabolism, pathology Opisthorchis RNA, Messenger / biosynthesis Urokinase-Type Plasminogen Activator / metabolism rac1 GTP-Binding Protein / biosynthesis, genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/RNA, Messenger; 9007-34-5/Collagen; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 3.4.21.73/Urokinase-Type Plasminogen Activator; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 3.6.5.2/rac1 GTP-Binding Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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