{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:07:03Z","timestamp":1780063623307,"version":"3.54.0"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2010,2,16]],"date-time":"2010-02-16T00:00:00Z","timestamp":1266278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2010,2,16]],"date-time":"2010-02-16T00:00:00Z","timestamp":1266278400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Peribiliary fibrosis caused by chronic infection with\n                    <jats:italic>Opisthorchis viverrini<\/jats:italic>\n                    (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                    <jats:italic>N<\/jats:italic>\n                    \u2010nitrosodimethylamine (NDMA). We assessed the time profiles of MMPs, inducible nitric oxide synthase (iNOS), Rac1, \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) and DNA lesions (8\u2010nitroguanine and 8\u2010oxo\u20107,8\u2010dihydro\u20102\u2032\u2010deoxyguanosine, 8\u2010oxodG) in relation to fibrosis and CCA development. Histopathology revealed OV and NDMA synergistically induced peribiliary fibrosis time\u2010dependently, 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 \u03b1\u2010SMA. MMP\u20109 expression was significantly increased and correlated with the accumulation of myofibroblast, fibrosis levels and cholangiocarcinogenesis. MMP\u20109 activity was correlated with iNOS, and immunocolocalization was observed in inflammed tissues, early and invasive CCA. OV and NDMA synergistically induced MMP\u20109 expression in association to Rac1. In addition, Rac1 was colocalized with iNOS, and 8\u2010nitroguanine, in inflammed tissues and CCA. Formation of 8\u2010nitroguanine and 8\u2010oxodG increased with tumor progression. The results suggest that MMP\u20109 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.\n                  <\/jats:p>","DOI":"10.1002\/ijc.25266","type":"journal-article","created":{"date-parts":[[2010,2,16]],"date-time":"2010-02-16T11:21:42Z","timestamp":1266319302000},"page":"2576-2587","source":"Crossref","is-referenced-by-count":83,"title":["Involvement of MMP\u20109 in peribiliary fibrosis and cholangiocarcinogenesis\n                    <i>via<\/i>\n                    Rac1\u2010dependent DNA damage in a hamster 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