Inhibitory effects of novel E2F decoy oligodeoxynucleotides on mesangial cell proliferation by coexpression of E2F/DP

Kwan-Kyu ParkJong Deok AhnIn-Kyu LeeJunji MagaeNicholas H.HeintzJong-Young KwakYoung-Choon LeeYoung-Su ChoHyun-Chul KimYoung-Mi ChaeYoung Ho KimCheorl-Ho KimYoung-Chae Chang
Dept. of Internal Medicine (내과학); Dept. of Pathology (병리학); Kidney Institute (신장연구소)
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Biochemical and Biophysical Research Communications, Vol.308(4) : 689-697, 2003
Proliferation of glomerular mesangial cells (MCs) is an important feature of several forms of glomerulonephritis. The transcription factor E2F coordinately regulates expression of genes required for cell proliferation, thereby mediating cell growth control. Here we investigated the role of E2F1 and E2F4 expression, with or without co-expression of DP1 or DP2, on cell proliferation in transiently transfected primary rat MCs. In transfected cells, cell proliferation induced by over-expression of E2F was significantly enhanced by co-expression of DP proteins. Previous studies showed that the transfection of decoy oligodeoxynucleotides (ODNs) corresponding to E2F binding sites inhibits cell proliferation. Here we have developed a Ring-E2F (R-E2F) decoy ODN with a circular dumbbell structure and compared its effects with those of a phosphorothioated E2F decoy (PS-E2F decoy) ODN. The R-E2F decoy ODN showed enhanced stability in the presence of nucleases and sera, and inhibited E2F/DP-dependent promoter activity of cell cycle genes more effectively than the PS-E2F decoy ODN. Transfection of R-E2F decoy ODN resulted in strong inhibition of cell cycle gene expression and MC proliferation. Our data suggest that E2F/DP complexes play a critical role in the MC proliferation and that the R-E2F decoy ODN may be a powerful tool for inhibiting cell proliferation. Keywords E2F; Dihydrofolate reductase; Decoy; Dumbbell; Mesangial cell proliferation
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1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
1. Journal Papers (연구논문) > 3. Research Institutues (연구소) > Kidney Institute (신장연구소)
Keimyung Author(s)
박관규; 김현철; 이인규
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