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Effect of Antisense TGF-β1 Oligodeoxynucleotides in Streptozotocin-Induced Diabetic Rat Kidney

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Affiliated Author(s)
최인장박관규김상표이인규김현철
Alternative Author(s)
Choi, In JangPark, Kwan KyuKim, Sang PyoLee, In KyuKim, Hyun Chul
Journal Title
Journal of Korean Medical Science
ISSN
1011-8934
Issued Date
2004
Keyword
Transforming Growth FactorsDiabetes MellitusOligonucleotidesStreptozotocin
Abstract
Transforming growth factor (TGF)- 1 is an important fibrogenic factor that is involved
in the pathogenesis of diabetic nephropathy. We evaluated the effect of circular
antisense TGF- 1 oligodeoxynucleotides (ODNs) on the TGF- 1 expression
in the rat mesangial cell culture and in streptozotocin (STZ)-induced diabetic rats.
Circular antisense TGF- 1 ODNs were found to be stable in rat serum, significantly
decreasing TGF- 1 mRNA expression compared with linear antisense ODNs in
the rat mesangial cell culture. Circular antisense TGF- 1 ODNs were introduced
into the tail vein of normal rats using hemagglutinating virus of Japan (HVJ)-liposomemediated
gene transfer method and were confirmed to be delivered effectively into
the kidney, liver, lungs, and spleen. To inhibit the overexpression of TGF- 1 in diabetic
kidneys, we introduced circular antisense TGF- 1 ODNs into the STZ-induced
diabetic rats. On day 13 after circular antisense TGF- 1 ODNs injection, TGF- 1
mRNA and protein expression markedly decreased and urinary TGF- 1 excretion
rate also dropped in the circular antisense TGF- 1 ODNs-treated diabetic rats.
These results suggest that circular antisense TGF- 1 ODNs may be a useful tool
for developing new therapeutic application for progressive diabetic nephropathy.
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