title: Prevention of tissue injury by ribbon antisense to TGF-beta1 in the kidney.
abstract: Transforming growth factor-beta1 (TGF-beta1) is an important mediator of glomerulosclerosis and tubulointerstitial fibrosis in renal diseases. We designed ribbon-type antisense oligos of TGF-beta1, TGF-beta1 RiAS, and combined them with a short peptide of the nuclear localization signal to form a transfection complex of DNA/peptide/liposomes (DPL) for enhanced cellular uptake. When H4IIE cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was reduced by >70%. We then examined the ratio of the kidney weight per body weight in rats. Whereas the weight ratio was 0.47% for the normal kidney, the ratio was 0.99% on day 5 after unilateral ureteric obstruction (UUO). The ratios were 0.95% with PBS injection, 1.07% with scrambled RiAS, and 0.68% with TGF-beta1 RiAS. When examined for TGF-beta1 expression in the tissue, the level of TGF-beta1 mRNA was also significantly reduced following treatment with TGF-beta1 RiAS. Further, physical changes such as diminished dilation, atrophy, as well as apoptosis caused by UUO were also found to be markedly reduced by TGF-beta1 RiAS. The results show that ribbon antisense to TGF-beta1 when combined with efficient uptake can effectively block TGF-beta1 expression and preserve tissue integrity in kidneys with UUO.
authors.affiliation: Department of Medical Genetic Engineering, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Young-Kook
authors.initials: YK
authors.lastname: Choi
authors.forename: Ik-Jae
authors.initials: IJ
authors.lastname: Moon
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Jung
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Jang
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Seo
authors.forename: Jong-Gu
authors.initials: JG
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D016373:DNA, Antisense / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*; D008081:Liposomes / Q000378:metabolism; D008297:Male; D009690:Nucleic Acid Conformation; D009929:Organ Size / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: D016373:DNA, Antisense; D008081:Liposomes; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1