| Project/Area Number |
17590668
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Nara Medical University |
|---|
Principal Investigator |
YOSHIJI Hitoshi Nara Medical University, 医学部, Lecturer (40336855)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Hideyuki Nara Medical University, 医学部, Same as head investigator (60326345)
TOYOHARA Masahisa Nara Medical University, 医学部, Same as head investigator (50336856)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,670,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | VEGF / Angiogenesis / Angiotensin-II |
|---|
| Research Abstract |
In the current project, we further explored to reveal a pivotal role of VEGF (vascular endothelial growth factor) in the progression of chronic liver diseases, such as liver fibrosis development and hepatocarcinogenesis. We first reported that angiopoietin synergistically augments VEGF-mediated hepatocellular carcinoma (HCC) development and angiogenesis. This orchestration of proangiogenic activity was exerted only in the presence of VEGF via induction of MMP-2 and MMP-9 in the tumor. In addition to the chronic liver diseases progression, we showed that VEGF plays a pivotal role in the hepatic regeneration after acute hepatic failure. Furthermore, we revealed that, as well as VEGFR-2, VEGFR-1 also exerted an important role in HCC development, and leptin-mediated neovascularization coordinated with VEGF plays an important role in the development of liver fibrosis development and hepatocarcinogenesis in non-alcoholic steatohepatitis (NASH). For a translational research, we reported that the combination treatment of angiotensin-II suppressing agent, such as angiotensin-converting enzyme inhibitor, and several agents (IFN and vitamin K) significantly suppressed the liver fibrosis and hepatocarcinogenesis both in the basic study and clinical practice. We published these data in several scientific journals, such as Hepatology and Gut.
|
