AP-1 transcription factor decoy reduces the TGF-beta1-induced cell growth in scleroderma fibroblasts through inhibition of cyclin E.
The transforming growth factor-beta (TGF-beta) signaling pathway plays a key role in the abnormal accumulation of type I and III collagen of scleroderma. Activator protein-1 (AP-1) is a key regulatory protein in TGF-beta1-induced type I collagen synthesis. However, it is largely unknown whether AP-1 is involved in the cell proliferation of fibroblasts in scleroderma. In this study, we investigated the effects of the AP-1 oligo-deoxynucleotide (ODN) decoy on TGF-beta1-induced cell growth in scleroderma fibroblasts. To investigate the inhibition of AP-1 ODN decoy on the growth rates of scleroderma fibroblasts through the regulation of cell cycle regulatory proteins, we transfected the AP-1 ODN decoy on scleroderma fibroblasts and analyzed the cell cycle regulatory proteins by RT-PCR and Western blot analysis. We found that the growth rates of normal fibroblasts and scleroderma fibroblasts showed similar rates. It is noteworthy that the scleroderma fibroblasts grew more rapidly than normal fibroblasts in the presence of TGF-beta1. Moreover, the transfection of AP-1 decoy ODN into scleroderma fibroblasts resulted in the down-regulation of the growth rates by the down-regulation of cyclin E. These results collectively suggest that AP-1 ODN decoy can down-regulate the growth rates of scleroderma fibroblasts, thus implying that AP-1 ODN decoy is a promising therapeutic tool for overcoming scleroderma.
Cho
Jae-We
JW
Department of Dermatology, Keimyung University School of Medicine, Daegu 700-712, Korea.
Cha
Young-Chang
YC
Lee
Kyu-Suk
KS
D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D019927:Cyclin E / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D018797:Cell Cycle Proteins; D024042:Collagen Type I; D019927:Cyclin E; D009838:Oligodeoxyribonucleotides; D018808:Transcription Factor AP-1; D053773:Transforming Growth Factor beta1