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

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

Objective To detect the expression of cell cycle positive regulators cyclin D(1), cyclin E , CDK(2), CDK(4) and negative regulators p21(cip1), p27(kip1), p16(in k4a) and p15(ink4b1) 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 D(1), cyclin E, CDK(2), CDK(4) and p21(cip1), p27(kip1), p16(ink4a), p15(ink4b1) 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 D(1), CDK(2) a nd CDK(4) 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(ink4a) and p15(ink4b1) 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.