| Research Abstract |
The present research project was designed to examined the availability of adenovirus vector for gene therapy for renal disease.
The data obtained during 1995-1996 is described below : 1.The preparation of adnovirus vector. We made the adenovirus vector containing the coding region of rat hepatocyte growth factor (HGF) in collaboration with Dr H.Hamada of Cancer Institute. 2.The application of adenovirus vector into the rat. In attempts to develop the method for the efficient application to the rat, we tried to apply the vector through intra-arterial, direct, intra-benous, and intra-urethreal approach. 3.Detection of gene expression. To detect the genes which adenovirus vector encode, Northern blot analysis or immunohistochemical staining method was used 2-8 weeks after the gene transfer. With these method, the amount of gene expression was not sufficient for the practical level required for gene therapy, which results were in accordance with reports from other institutes. These findings
… More
suggest that adenovirus vector has some limitation for the clinical use for gene therapy. 4.Clinical investigation. We measured the plasma level of HGF to evaluate the clinical implication of HGF in the development of chronic renal failure. The result indicate that plasma HGF level was increased in patients of end stage renal disease, suggesting that HGF might act as an endogenously produced renal protecting factor. Plasma HGF level was also increased in renal transplantation recipients, of which clinical implication should be investigated further. 5.Molecular mechanism for the development of chronic renal failure. To elucidate the molecular basis for the development of chronic renal failure, vascular smoothe muscle cells and mesangial cells were cultured on flexible bottome dish, on which cell were constantly exposed to cyclic stretch/relaxation. These cells expressed PHTrP or TGF-b mRNA in response to stretch, which implys a role of glomerular hypertension in the development glomerular sclerosis. Less
|
