Inhibition of G1 Cell Cycle Arrest in Human Gingival Fibroblasts Exposed to Phenytoin
Inhibition of G1 Cell Cycle Arrest in Human Gingival Fibroblasts Exposed to Phenytoin
复制标题
苯妥英对人牙龈成纤维细胞 G1 细胞周期停滞的抑制
DOI：
10.1111/j.1472-8206.2012.01065.x
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Reiri Takeuchi，Hiroko Matsumoto， Yoshiaki Akimoto，Akira Fujii
中科院分区：
文献类型：
--
作者：
Takeda M;Takahashi M;Nasu M;Matsumoto S.;Reiri Takeuchi，Hiroko Matsumoto， Yoshiaki Akimoto，Akira Fujii
牙龈过度生长是由抗癫痫药物苯妥英(PHT)引起的。PHT诱导的牙龈过度生长的特征是成纤维细胞的增殖和牙龈中胶原的形成增加。成纤维细胞的增殖通过细胞周期进行调节。因此，在本研究中，我们检测了PHT对人牙龈成纤维细胞(HGFs)细胞周期、细胞周期调控蛋白表达和增殖的影响。细胞在无血清的DMEM中刺激，加或不加0.25mPHT的μ。观察24、48、72 h后细胞周期时相分布、蛋白表达及细胞增殖情况。PHT通过血清饥饿显著抑制HGFs细胞周期G0/G1期的同步化。PHT刺激48h和72h可显著诱导HGFs的增殖反应。PHT降低无血清DMEM中CDK抑制蛋白p21和p27的表达，上调S相促进蛋白磷酸化Thr160-CDK2和磷酸化Ser807/811-Rb的水平。PHT可能通过增加CDK2和Rb蛋白的磷酸化水平，降低p21和p27蛋白的水平，从而抑制HGFs的G1期细胞周期。牙周过度生长可能是由于PHT诱导的GFS细胞G1期停滞失败所致。
Gingival overgrowth is caused in response to the antiepileptic drug phenytoin (PHT). PHT‐induced gingival overgrowth is characterized by the proliferation of fibroblasts and increased collagen formation in gingiva. Fibroblast proliferation is regulated through the cell cycle. Thus, in the present study, we examined the effects of PHT on the cell cycle, the expression of cell cycle control proteins and the proliferation in human gingival fibroblasts (hGFs). Cells were stimulated in serum‐free DMEM with or without 0.25 μmPHT. Subsequently, the cell cycle phase distribution and the protein expression after 24 h and the cell proliferation after 24, 48 and 72 h were evaluated. PHT significantly inhibited synchronization at the G0/G1phase of the cell cycle in hGFs through serum starvation. Stimulation with PHT for 48 and 72 h significantly induced a proliferative response in hGFs. PHT decreased the expression of the Cdk‐inhibitory proteins p21 and p27 and increased the levels of the S phase‐promoting proteins phospho‐Thr160‐Cdk2 and phospho‐Ser807/811‐Rb in serum‐free DMEM. The inhibition of G1cell cycle arrest in hGFs may result from an increase in phosphorylated Cdk2 and Rb proteins and decreased levels of p21 and p27 proteins by PHT. The gingival overgrowth may be caused by the failure of the G1 cell cycle arrest in GFs exposed to PHT.