کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9245186 | 1209942 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cell Type-Specific Intervention of Transforming Growth Factor β/Smad Signaling Suppresses Collagen Gene Expression and Hepatic Fibrosis in Mice
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Cell Type-Specific Intervention of Transforming Growth Factor β/Smad Signaling Suppresses Collagen Gene Expression and Hepatic Fibrosis in Mice Cell Type-Specific Intervention of Transforming Growth Factor β/Smad Signaling Suppresses Collagen Gene Expression and Hepatic Fibrosis in Mice](/preview/png/9245186.png)
چکیده انگلیسی
Background & Aims: Transforming growth factor β and its intracellular mediators, Smad proteins, play important roles in stimulating collagen gene transcription and, thus, could be the targets for treating hepatic fibrosis. However, intervention of transforming growth factor β/Smad signaling affects physiological signal transduction as well and may cause serious adverse effects on clinical application. Here we have attempted to suppress hepatic fibrosis by expressing a transforming growth factor β/Smad antagonist selectively in collagen-producing cells only in the fibrotic liver. Methods: Recombinant adenoviruses expressing either green fluorescent protein or a transforming growth factor β/Smad signal repressor, YB-1, were injected into mice untreated or treated with carbon tetrachloride. Green fluorescent protein expression was analyzed under a confocal laser scanning microscope. Antifibrotic effects of YB-1 overexpression were examined by luciferase assays and histological examination with transgenic reporter mice. Results: When the CAG expression unit was used as a control, green fluorescent protein was strongly expressed in a large number of hepatocytes in both normal and carbon tetrachloride-treated liver. In contrast, green fluorescent protein expression driven by a tissue-specific enhancer of the mouse α2(I) collagen gene (COL1A2) was detected in activated hepatic stellate cells in carbon tetrachloride-induced fibrotic liver, but not in untreated normal liver. No green fluorescent protein fluorescence was observed in any other organs when the COL1A2 enhancer was used. Adenovirus-mediated YB-1 expression under the control of the COL1A2 enhancer significantly decreased COL1A2 promoter activity after carbon tetrachloride injection and subsequently suppressed the progression of hepatic fibrosis. Conclusions: These results validate a new concept of the therapy for hepatic fibrosis to achieve cell type-specific gene expression only in the fibrotic liver, with little damage to other organs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 129, Issue 1, July 2005, Pages 259-268
Journal: Gastroenterology - Volume 129, Issue 1, July 2005, Pages 259-268
نویسندگان
Yutaka Inagaki, Miwa Kushida, Kiyoshi Higashi, Johbu Itoh, Reiichi Higashiyama, Yun Yu Hong, Norifumi Kawada, Kazuhiko Namikawa, Hiroshi Kiyama, George Bou-Gharios, Tetsu Watanabe, Isao Okazaki, Kazuo Ikeda,