Cell Growth and Cell Cycle in Nifedipine-Reactive Human Gingival Fibroblasts

硝苯地平反应性人牙龈成纤维细胞的细胞生长和细胞周期

• 批准号: 13671983
• 负责人: FUJII Akira
• 金额: $ 1.92万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671983/
• 关键词: nifedipine; gingival fibroblast; cell cycle; cell growth; cyclin; cyclin-dependent kinase (CDK); gingival overgrowth; bFGF; 細胞内情報伝達; p38MAPK; カルシウム拮抗薬; 歯肉増殖症; 歯肉培養線維芽細胞

The objective of the present study was to characterize the differences in cell cycle between nifedipine responder (NIFr) and non-responder (NIFn) gingival fibroblasts. The progression of S and G2/M phases in NIFr was greater than those in NIFn in the presence of 10% fetal calf serum. NIFn cells possessed more p38 MAPK activity in resting state and more sensitive to NIF in expression of p38 MAPK. The percentage of ATF-2 phosphorylation treated by Anisomysin or IBMX (3-isobutyl-1-methylxanthine) in NIFn cells was greater than those in NIFr cells. Since p38 MAPK, that might exist and play an important role on the depression of cell cycle progression, these results suggest NIFn cells have less mitotic activity than NIFr cells. Thus, fibroblasts in NIFn might be depressed cell cycle progression resulting in lesser amount of fibroblasts present in gingival tissue. Nifedipine (NIF) did not alter any change on mRNA expression of cyclins A, B1, D1, E in both of NIFr and NIFn. However, a greater number of NIFr than NIFn cells underwent progression to S and G2/M phases from G0/G1 phase in the presence of basic fibroblast growth factor (bFGF). mRNA expression of cyclins A, B1, D1, E and CDKs 1, 2, 4, 6 in the presence of 10 ng/ml bFGF was generally greater in NIFr cells than NIFn cells. These results indicate that NIFr cells may be more susceptible to growth factors such as bFGF with a resultant increase in expression of cyclins and CDKs in NIFr cells compared with NIFn cells.

本研究的目的是表征硝苯地平应答者（NIFr）和非应答者（NIFn）牙龈成纤维细胞之间细胞周期的差异。在10%胎牛血清存在下，NIFr的S期和G2/M期进展大于NIFn。NIFn细胞在静息状态下p38 MAPK活性增强，对NIF的敏感性增强。在NIFn细胞中，经山莨菪碱或IBMX（3-异丁基-1-甲基黄嘌呤）处理的ATF-2磷酸化的百分比大于在NIFr细胞中的那些。由于p38 MAPK可能存在并在抑制细胞周期进程中起重要作用，这些结果表明NIFn细胞的有丝分裂活性低于NIFr细胞。因此，NIFn中的成纤维细胞可能被抑制细胞周期进程，导致牙龈组织中存在较少的成纤维细胞。硝苯地平（NIF）对NIFr和NIFn细胞周期蛋白A、B1、D1、E的mRNA表达无明显影响。然而，在碱性成纤维细胞生长因子（bFGF）的存在下，NIFr细胞比NIFn细胞更多地经历从G 0/G1期到S和G2/M期的进展。在10 ng/ml bFGF存在下，NIFr细胞中细胞周期蛋白A、B1、D1、E和CDKs 1、2、4、6的mRNA表达通常高于NIFn细胞。这些结果表明，与NIFn细胞相比，NIFr细胞可能对生长因子如bFGF更敏感，从而导致NIFr细胞中细胞周期蛋白和CDK的表达增加。

项目成果

Reiri Takeuchi: "The effect of basic fibroblast growth factor on cell cycle in human gingival fibroblasts from nifedipine responder and non-responder."Journal of Oral Science. 46(1). 37-44 (2004)

Reiri Takeuchi：“碱性成纤维细胞生长因子对硝苯地平应答者和非应答者牙龈成纤维细胞细胞周期的影响。”口腔科学杂志。