Gene therapy of chronic liver injury with RNAi vector targeting TGF-beta receptor
| Project/Area Number |
16591364
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
TAJIRI Takashi Nippon Medical School, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (20163462)
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| Co-Investigator(Kenkyū-buntansha) |
AKIMARU Koho Nippon Medical School, Faculty of Medicine, Professor, 医学部, 教授 (40142541)
ARIMA Yasuo Nippon Medical School, Faculty of Medicine, Assistant Professor, 医学部, 講師 (30168025)
YOSHIDA Hiroshi Nippon Medical School, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60246999)
YOKOMURO Shigeki Nippon Medical School, Faculty of Medicine, Assistant Professor, 医学部, 講師 (30267223)
MIZUGUCHI Yoshiaki Nippon Medical School, Graduate School of Medicine, Post doctor, 大学院・医学研究科, ポストドクター (70409217)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | RNA interference / liver injury / gene therapy / TGF beta / TGF beta receptor II / TGF-β recepter II |
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| Research Abstract |
Transforming growth factor beta (TGF-B) receptor II (TGF-BRII), which is essential for TGF-B signaling and is involved in the causation or participates in the pathway of various human disorders, is consequently considered a key target for therapeutics and analysis of the pathophysiology associated with disruption of the TGF-B system. In the liver, TGF-B plays an essential role in hepatocyte apoptosis, growth inhibition, and progression of fibrogenesis. There is a critical need to introduce technology involving the TGF-B system, such as RNA interference (RNAi), which has high potential for in vivo therapeutics and analytical activities. Here, we investigated the effect of short hairpin RNA targeting TGF-BRII, using hepatocyte injury in human and mouse cell lines and liver injury mouse models. We demonstrated that short hairpin RNA targeting TGF-BRII can be used to silence TGF-BRII genes in mouse and human cell lines, and physiologic and morphologic changes in hepatocytes suffering from acute injury are spared by RNAi-mediated gene silencing of the target gene and by suppressing downstream signal transduction. Furthermore, short hairpin RNA targeting TGF-BRII protected mice from life-threatening acute liver failure.
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Report
(3 results)
Research Products
(3 results)
