| Project/Area Number |
11670500
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
TAMURA Shinji Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30243223)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ITO Nobuyuki Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30273668)
INUI Yoshiaki Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (00294067)
KAWATA Sumio Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90183285)
KISO Shinichi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | soluble-HB-EGF / liver regeneration / in vivo / HVJ-liposome / gene therapy / hepatocyte / growth factor / HB-EGF |
|---|
| Research Abstract |
We have reported that heparin-binding EGF-like growth factor (HB-EGF) is a potent mitogen of hepatocytes in vitro. The level of HB-EGF mRNA in regenerating rat liver creases rapidly after a partial hepatectomy. In vitro study showed that HB-EGF induces the expression of HGF and TGF-alpha in non-parenchymal cells and hepatocytes, respectively. To clarify the role of soluble-HB-EGF, we studied the effect of an inhibitor which inhibits the post-tanslational processing from a membrane-bind form of HB-EGF to a soluble form, using HB-EGF transgenic mouse. The inhibitor decreased the labeling index of hepatocyte, indicating that soluble-HB-EGF is important in liver regeneration. We also investigated the effect of administration of soluble-HB-EGF to mice on proliferation of hepatocyte in vivo. Recombinant soluble-HB-EGF was administered intravenously to the normal mice for 4 times at 2h-interval. The labeling index is 300-fold higher in HB-EGF administered mice than that of controls. In vivo administration of HB-EGF activated NF-kB and STAT-3 in the liver. The induction of HGF was observed in HB-EGF-administered mice liver. To develop gene therapy of soluble-HB-EGF using HVJ-liposome method, we administered the HVJ-liposome to mouse intravenously. No serious adverse effect was observed by the administration. Injection of expression plasmid containing soluble-HB-EGF gene in HVJ-liposome in the *uscle of mouse increased the plasma levels of HB-EGF.These results indicated that introduction of soluble HB-EGF gene using HVJ-liposome method could be a candidate for new approach to accelerate the liver regeneration
|
