title: Effect of antisense TGF-beta1 oligodeoxynucleotides in streptozotocin- induced diabetic rat kidney.
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.
authors.affiliation: Department of Anatomy, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Hyo Soon
authors.initials: HS
authors.lastname: Jeong
authors.forename: Kwan Kyu
authors.initials: KK
authors.lastname: Park
authors.forename: Kwan Kyu
authors.initials: KK
authors.lastname: Park
authors.forename: Sang Pyo
authors.initials: SP
authors.lastname: Kim
authors.forename: In Jang
authors.initials: IJ
authors.lastname: Choi
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Kim
mesh_terms: 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
chemical_list: 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