2002 Fiscal Year Final Research Report Summary
Study on gene therapy for liver regeneration. -Effect of gene transduction of soluble HB-EGF and soluble TGF-β type II receptor on liver regeneration-
| Project/Area Number |
13670517
|
|---|
| 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) |
IGURA Takumi Osaka University Hospital, Medical Staff, 医学部附属病院, 医員(臨床研究)
FUKUI Koji Osaka University Hospital, Medical Staff, 医学部附属病院, 医員(臨床研究)
KISO Shinichi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40335352)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | liver regeneration / soluble receptor / soluble HB-EGF / TGF-β / gene therapy |
|---|
| Research Abstract |
Acceleration of liver regeneration is important for the treatment of hepatic failure. We have reported that HB-EGF is a potent mitogen of hepatocyte and plays an important role in liver regeneratian. On the other hands, TGF-β, a growth inhibitory factor stimulates apoptosis of hepatocyte and inhibits liver regeneration.
In this study, we demonstrated that NF-kB is activated in hepatic non-parenchymal cells after partial hepatectomy and stimulates the expression of HB-EGF gene. We also indicated that soluble form of HB-EGF is essential for liver regeneration using HB-EGF transgenic mice.
To develop the new methods for acceleration the liver regeneration, dual introduction of soluble HB-EGF gene and soluble TGF-βtype II receptor that blocks the action of TGF-β is investigated. We developed the expression plasmid containing soluble TGF-βtype II receptor cDNA attached with human immunoglobulin Fc region or soluble HB-EGF cDNA. Both genes were introduced into mice skeletal muscle using in vivo electroporation methods. The plasma concentration of soluble HB-EGF and soluble TGF-β type II receptor were measured with newly developed ELISA systems. Pretreatment with hyaluronidase increased the expression levels and obtains 6-fold higher concentrations of soluble HB-EGF or soluble TGF-βtype II receptor.
Our results give a basis for development of the gene therapy to accelerate the liver regeneration.
|
Research Products
(6 results)
-
-
-
-
[Publications] S. Sakuda, S. Tamura, A. Yamada, J. Miyagawa, K. Yamamoto, S. Kiso, N. Ito, S. Higashiyama, N. Taniguchi, S. Kawata, Y. Matsuzawa: "NF-kappaB activation in non-parenchymal liver cells after partial hepatectomy in rats: possible involvement in expression of heparin-binding epidermal growth factor-like growth factor"J Hepatol.. 36(4). 527-533 (2002)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] S. Sakuda, S. Tamura, A. Yamada, J. Miyagawa, K. Yamamoto, S. Kiso, N. Ito, K. Imanaka, A. Wada, T. Naka, T. Kishimoto, S. Kawata, Y. Matsuzawa: "Activation of signal transducer and activator transcription 3 and expression of suppressor of cytokine signal 1 during liver regeneration in rats"J Hepatol.. 36(3). 378-384 (2002)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] S. Kiso, S. Kawata, S. Tamura, Y. Inui, Y. Yoshida, Y. Sawai, S. Umeki, N. Ito, A. Yamada, J. Miyagawa, S. Higashiyama, T. Iwawaki, M. Saito, N. Taniguchi, Y. Matsuzawa, K. Kohno: "Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy"Gastroenterology. 124(3). 701-707 (2003)
Description
「研究成果報告書概要(欧文)」より
