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Role and Mechanism of c-ski on Proliferation of Rat Skin-derived Fibroblast
Xia Liu, Ping Li, En Zhang, Ping Liu, Ping Zhou, Yuan-Guo Zhou*
Molecular Biology Center, Research Institute of Surgery and Daping Hospital, the Third Military Medical University, Chongqing 400042, China
Abstract: 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 modulator 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.