Effect of antisense TGF-beta1 oligodeoxynucleotides in streptozotocin- induced diabetic rat kidney.
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.
Jeong
Hyo Soon
HS
Department of Anatomy, Keimyung University School of Medicine, Daegu, Korea.
Park
Kwan Kyu
KK
Park
Kwan Kyu
KK
Kim
Sang Pyo
SP
Choi
In Jang
IJ
Lee
In Kyu
IK
Kim
Hyun Chul
HC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D007150:Immunohistochemistry; D008081:Liposomes / Q000737:chemistry; D008297:Male; D018613:Microscopy, Confocal; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D001786:Blood Glucose; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013311:Streptozocin; D012313:RNA