Gene transfer and kidney disease.
There is little doubt that molecular biological intervention therapy has come of age and its potential is arousing tremendous excitement. A gene transfer technique, the HVJ-liposome method, is now applicable as a tool for the dissection of molecular aspects in the pathophysiology of renal diseases, and for gene therapy in experimental glomerulonephritis. Overexpressed transforming growth factor (TGF)-beta in the normal rat glomeruli, by gene transfer of TGF-beta cDNA, leads to glomerulosclerosis. However, inhibition of the TGF-beta action by antisense oligonucleotides can suppress the development of the experimental glomerulonephritis. We investigated whether in vivo gene transfer of chimeric proteins, composed of the extracellular domain of TGF-beta type II receptor fused with IgC-Fc, suppresses experimental glomerulonephritis. The expression of TGF-beta in glomeruli was suppressed and so was the extracellular matrix expansion. Taken together with clinical observation of up-regulation of TGF-beta in various glomerulopathies, the dys-regulation of the TGF-beta is important in the development of glomerulosclerosis, and manipulation of this overexpression may prove a novel therapeutic approach for slowing the progression of the disease.
Imai
E
E
Osaka University School of Medicine, Japan.
Isaka
Y
Y
Akagi
Y
Y
Kaneda
Y
Y
Hori
M
M
D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007674:Kidney Diseases / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D018108:Respirovirus / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*
D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta