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Elucidation of the role of COX-2 in liver fibrogenesis using transgenic mice (2008)_香港中文大学化學病理學系 (CP

香港中文大学 辅仁网/2017-06-20

Elucidation of the role of COX-2 in liver fibrogenesis using transgenic mice
Publication in refereed journal


香港中文大学研究人员 ( 现职)
于君教授 (内科及药物治疗学系)
沈祖尧教授 (内科及药物治疗学系)
陈力元教授 (内科及药物治疗学系)
崔耀隆教授 (化学病理学系)
吴燕燕医生
郑诗乐教授 (生物医学学院)
许睿教授 (内科及药物治疗学系)
朱少康先生 (内科及药物治疗学系)
吴宗华博士 (内科及药物治疗学系)


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Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/18WOS source URL

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摘要Hepatic COX-2 overexpression is sufficient to induce hepatitis, but its role on liver fibrosis remains unknown. We aim to elucidate possible biological effects of COX-2 in liver fibrosis using both gain-of-function and loss-of-function mouse models. COX-2 transgenic (TG) mice that specifically overexpress the human COX-2 cDNA in the liver, knockout (KO), and wild type (WT) mice were studied in two different murine fibrosis models induced by carbon tetrachloride (CCl4) injection or methionine and choline-deficient (MCD) diet. Liver injury was assessed by serum ALT and bilirubin levels and histological examination. Hepatic collagen content was determined by picrosirius red stain morphometry assay and quantitation of hydroxyproline. Hepatic stellate cell (HSC) activation was determined by immunohistochemical analysis of alpha-smooth muscle actin (alpha-SMA). mRNA expression of fibrogenic genes was assayed by real-time quantitative PCR. COX-2 protein was overexpressed in the liver of TG mice compared with WT littermates. CCl4 or MCD-induced liver fibrotic injury was equally severe in TG and WT mice, as demonstrated by similar elevated levels of hepatic collagen contents. Enhanced COX-2 expression in TG liver did not affect HSC activation and fibrogenic gene expression upon CCl4 or MCD treatment. Importantly, CCl4-treated KO mice did not show significant difference in liver fibrotic damage and fibrogenic gene expression compared with the WT counterparts. This is the first report on the effect of COX-2 in liver fibrosis based on genetic mouse models. The results suggest that COX-2 does not appear to mediate the development of liver fibrosis. (C) 2008 Elsevier Inc. All rights reserved.

着者Yu J, Wu CW, Chu ESH, Hui AY, Cheng ASL, Go MYY, Ching AKK, Chui YL, Chan HLY, Sung JJY
期刊名称Biochemical and Biophysical Research Communications
出版年份2008
月份8
日期8
卷号372
期次4
出版社Elsevier
页次571 - 577
国际标準期刊号0006-291X
电子国际标準期刊号1090-2104
语言英式英语

关键词COX-2; fibrotic factors; liver fibrosis; transgenic mouse model
Web of Science 学科类别Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Biophysics; BIOPHYSICS

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