Expression of positive and negative regulators of cell cycle during wound healing

Objective To detect the expression of cell cycle positive regulators cyclin D1, cyclin E , CDK2, CDK4 and negative regulators p21 cip1 , p27 kip1 , p16 in k4a and p15 ink4b during wound healing in rats. Methods Open wounds of full-thickness skin, diameter 1.8?cm, on rat backs were used a s the wound model. Wound tissues were harvested on postwounding days 3, 5, 7, 9 , 11, 14, 21 and 30. Ki67 expression in granulation tissue was detected by immu nohistochemical assay. The patterns of the expression of cyclin D1, cyclin E, CDK2, CDK4 and p21 cip1 , p27 kip1 , p16 ink4a , p15 ink4b were detected by Western blot. Results Cell proliferation in granulation tissue took place predominantly within the fir st week after injury, with the proliferation peak occurring at postwounding day 5. There were no dramatic variations in the expression of cyclin D1, CDK2 a nd CDK4 during wound healing. Up-regulated cyclin E was maintained from day 3 to 11 after injury, and then was down-regulated. No expression of p16 ink 4a and p15 ink4b was found. p21 cip1 was expressed only from day 7 to 14, with peak expression observed on day 9. Constitutive p27 kip1 was e xpressed throughout wound healing with low levels in the proliferating period of day 3 to 5 and with increased levels in the post-mitotic and remodeling stage . The expression of p21 cip1 and p27 kip1 showed an inverse gradient to that of Ki67. Conclusion p21 cip1 and p27 kip1 play a supervising role in preventing the hyperp roliferative tendency in tissue repair.