c-ski对大鼠皮肤成纤维细胞增殖的调节作用及机制

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-ski mRNA表达在加入血清后开始升高，在细胞周期G，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。

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

c-ski is a complex modulator of fibroblast proliferation. How it affects proliferation of mesoderm- derived 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.