Effect of Antisense TGF-beta1 Oligodeoxynucleotides in Streptozotocin-Induced Diabetic Rat Kidney
Journal of Korean Medical Science
; : 374-383, 2004.
Article
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| WPRIM
| ID: wpr-124477
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WPRO
ABSTRACT
Transforming growth factor (TGF)-beta1 is an important fibrogenic factor that is involved in the pathogenesis of diabetic nephropathy. We evaluated the effect of circular antisense TGF-beta1 oligodeoxynucleotides (ODNs) on the TGF-beta1 expression in the rat mesangial cell culture and in streptozotocin (STZ)-induced diabetic rats. Circular antisense TGF-beta1 ODNs were found to be stable in rat serum, significantly decreasing TGF-beta1 mRNA expression compared with linear antisense ODNs in the rat mesangial cell culture. Circular antisense TGF-beta1 ODNs were introduced into the tail vein of normal rats using hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer method and were confirmed to be delivered effectively into the kidney, liver, lungs, and spleen. To inhibit the overexpression of TGF-beta1 in diabetic kidneys, we introduced circular antisense TGF-beta1 ODNs into the STZ-induced diabetic rats. On day 13 after circular antisense TGF-beta1 ODNs injection, TGF-beta1 mRNA and protein expression markedly decreased and urinary TGF-beta1 excretion rate also dropped in the circular antisense TGF-beta1 ODNs-treated diabetic rats. These results suggest that circular antisense TGF-beta1 ODNs may be a useful tool for developing new therapeutic application for progressive diabetic nephropathy.
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WPRIM
Asunto principal:
Factores de Tiempo
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Glucemia
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ARN
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ARN Mensajero
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Ensayo de Inmunoadsorción Enzimática
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Inmunohistoquímica
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Transfección
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Células Cultivadas
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Oligonucleótidos Antisentido
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Factor de Crecimiento Transformador beta
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Animals
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En
Revista:
Journal of Korean Medical Science
Año:
2004
Tipo del documento:
Article