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Gene transfer and kidney disease

Imai, E.; Isaka, Y.; Akagi, Y.; Kaneda, Y.; Hori, M.

Journal of Nephrology 11(1): 16-19

1998

ISSN/ISBN: 1121-8428
PMID: 9561480
Document Number: 497070
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.

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