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KMID : 0848120120370030115
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International Journal of Oral Biology
2012 Volume.37 No. 3 p.115 ~ p.120
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Retinoic Acid Increases the Cell Cycle Progression of Human Gingival Fibroblasts by Increasing Cyclin E and CDK 2 Expression and Decreasing p21WAF1/CIP1 and p16INK4A Expression
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You Hyung-Keun
Seo Se-Jeong
Kim Kang-Ju
Choi Na-Young
You Yong-Ouk
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Abstract
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Retinoic acid plays an important role in the regulation ofcell growth and differentiation. In our present study, weevaluated the effects of all-trans retinoic acid (RA) on cellproliferation and on the cell cycle regulation of humangingival fibroblasts (HGFs). Cell proliferation was assessedusing the MTT assay. Cell cycle analysis was performed byflow cytometry, and cell cycle regulatory proteins weredetermined by western blot. Cell proliferation was increasedin the presence of a 0.1 nM to 1μM RA dose range,and maximal growth stimulation was observed in cellsexposed to 1 nM of RA. Exposure of HGFs to 1 nM of RAresulted in an augmented cell cycle progression. Toelucidate the molecular mechanisms underlying cell cycleregulation by RA, we measured the intracellular levels ofmajor cell cycle regulatory proteins. The levels of cyclin Eand cyclin-dependent kinase (CDK) 2 were found to beincreased in HGFs following 1 nM of RA treatment.However, the levels of cyclin D, CDK 4, and CDK 6 wereunchanged under these conditions. Also after exposure to 1nM of RA, the protein levels of p21 WAF1/CIP1 and p16 INK4A were decreased in HGFs compared with the control group, but the levels of p53 and pRb were similar between treatedand untreated cells. These results suggest that RA increasescell proliferation and cell cycle progression in HGFs viaincreased cellular levels of cyclin E and CDK 2, anddecreased cellular levels of p21 WAF1/CIP1 and p16 INK4A .
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KEYWORD
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Retinoic acid, Cell cycle, Human gingival fibroblasts
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