Abstract
To analyze human diseases at molecular level and to promote gene therapy strategy, we developed HVJ-liposome gene delivery system. By the transfer of TGF-β gene to rat glomerulus using the system, glomerulosclerotic changes characterized by the accumulation of extracellular matrix were induced in rat kidney. To suppress TGF-β by antisense oligonucleotides in experimental glomerulonephritic rats, glomerulosclerotic changes were inhibited. Therefore, TGF-β appears to be responsible for the pathogenesis of glomerulosclerotic changes. Toward the gene therapy of glomerulosclerosis, decorin gene was introduced into nephritic rat muscle. Decorin was expressed in muscle and accumulated in glomerulus. By decorin gene transfer, TGF-β expression was suppressed in nephritic rat kidney and a number of TGF-β positive glomerulus was reduced to 40% compared with the rat treated with CAT gene. The accumulation of extracellular matrix proteins was decreased. These results indicate that decorin gene transfer to muscle will be promising for gene therauv of glomerulosclerosis.
