c-ski对大鼠皮肤成纤维细胞增殖的调节作用及机制  

Role and Mechanism of c-ski on Proliferation of Rat Skin-derived Fibroblast

作　　者：刘霞[1] 李平[1] 张恩[1] 刘萍[1] 周萍[1] 周元国[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所分子生物学中心,重庆400042

出　　处：《细胞生物学杂志》2005年第5期559-564,共6页Chinese Journal of Cell Biology

基　　金：国家重点基础研究发展规划项目(973计划)(No.G1999054205);国家自然科学基金项目(No.30400468)资助~~

摘　　要：c-ski是成纤维细胞增殖的复杂调节子,它对中胚层来源的皮肤成纤维细胞增殖的作用还不清楚。在观察正常成纤维细胞周期c-ski表达的时相特点的基础上,通过体外转染c-ski,观察它对细胞增殖活性、细胞周期进展以及周期蛋白表达的影响。结果显示:c-skimRNA表达在加入血清后开始升高,在细胞周期G1期的高峰期达到峰值,S期显著下降,在G2/M期维持在较低的水平;转染的c-ski可以以剂量依赖的方式增加细胞的增殖活性,并且可以逆转Smad3对细胞增殖活性的抑制作用;C-ski使成纤维细胞提前达到G0/G1期的最低点,进入S期;同时细胞G1期周期蛋白cyclinD的表达增加。这些结果表明:c-ski是皮肤成纤维细胞G1期的调节子,通过加快G1期进展促进增殖,抑制Smad3活性,促进cyclinD的表达可能与这一作用的分子机制有关。c-ski is a complex modulator of fibroblast proliferation. How it affects proliferation of mesodermderived skin fibroblast has not been defined. In our present study, on the base of observing the expression pattern of c-ski mRNA during normal cell cycle progression, by using c-ski gene transfection into skin fibroblast, we observed the changes of cell viability, cell cycle progression and cell cycle protein expression. The results showed that： upon stimulated by serum, the mRNA expression of c-ski began to increase and reached the highest level at G1 phase peak, then declined at S phase, and sustained low expression at G2/M phase, c-ski could increase cell proliferation viability in a dose-dependent manner, and could inverse the inhibitory effect of Smad3 on fibroblast proliferation.c-ski could make fibroblast ahead progress into the bottom of G0/G1 phase, then progress into S phase. Meanwhile, it promoted cyclinD, a G1-phase-related protein, to express. All these indicate that c-ski is a G1-phase-related modu- lator of skin-derive fibroblast. It can promote cell proliferation by accelerating G1 phase progression. Inhibiting Smad3 activity and promoting cyclinD expression may be responsible for role of c-ski in fibroblast proliferation.

关 键 词：c-ski 大鼠 皮肤成纤维细胞 细胞增殖 调节作用 调节机制 细胞周期 

分 类 号：S852.3[农业科学—基础兽医学]