2000 Fiscal Year Final Research Report Summary
A study of molecular diagnosis and treatment for chronic cardiac allograft rejection.
Grant-in-Aid for Scientific Research (B).
|Allocation Type||Single-year Grants |
|Research Institution||Osaka University |
SHIRAKURA Ryota Osaka University Graduate School of Medicine, Professor -> 大阪大学, 医学系研究科, 教授 (00116047)
FUKUSHIMA Norihide Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30263247)
SAWA Yoshiki Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00243220)
MIYAGAWA Shuji Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90273648)
SAKAKIDA Satoru Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90311753)
|Project Period (FY)
1998 – 2000
|Keywords||Chronic rejection / Rat / Heterotopic heart transplantation / Quantitative RT-PCR|
This study was performed as three parts described as below.
1 : We have measured the dynamics of 65 different immune gene expressions using real-time quantitative RT-PCR in retransplanted rat hearts developing cardiac allograft vasculopathy (CAV). This retransplantation model provided better opportunities to investigate the molecular mechanism, because the correlation between the occurrence of chronic rejection and the expression pattern of the identified gene was more stringent than those in other animal models. In summary of this part of the study, the importance of selective chemokine/receptor systems including IP10-CXCR3, RANTES-CCR5, and MCP1-CCR2 was indicated in addition to the implication of cytokines produced by activated T cells (IFN-γ and Fas ligand), growth factors for vascular smooth muscle cells (PDGF-β, TGF-β) in the progression of CAV.
2 : The developed technology using real-time RT-PCR was applied to the investigation of Myasthenia Gravis in clinical situation and provid
ed the data suggesting the implication of suppressed class II transactivator gene-expression of dysregulation of MHC class II antigen on thymoma cells in pathogenesis of the disease. This results also indicated the feasibility of this method in clinical diagnosis of various diseases includeing CAV.
3 : Experimental gene therapy was performed using beta-adrenergic receptor gene and hepatocyte growth factor gene. In both cases, ischemia-reperfusion injury was attenuated by the introduction of either gene into a whole heart in vivo. It is conceivable that the technique should provide the way to treat CAV in clinical situation, because CAV is a local disorder under systemic immunosuppression.
Clinical heart transplantation in Japan has just began and it was impossible to apply the technique developed in this study on the clinical diagnosis of chronic rejection as originally planed. Nonetheless, this study provided several new methods applicable to the diagnosis and the treatment of CAV in clinical situation. Less
Research Products (16 results)