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

细胞周期正负调控因子在伤口愈合中的表达规律及意义

作　　者：朱旭东[1] 邸雁飞[1] 胡承香[1] 王正国[1] 

机构地区：[1]第三军医大学野战外科研究所,重庆400042

出　　处：《Chinese Medical Journal》2002年第3期326-330,共5页中华医学杂志（英文版）

摘　　要：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(ink4a) and p15(ink4b) during wound healing in rats. METHODS: Open wounds of full-thickness skin, diameter 1.8 cm, on rat backs were used as 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 immunohistochemical assay. The patterns of the expression of cyclin D(1), cyclin E, CDK(2), CDK(4) 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 first 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) and 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(ink4b) was found. p21(cip1) was expressed only from day 7 to 14, with peak expression observed on day 9. Constitutive p27(kip1) was expressed 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 hyperproliferative tendency in tissue repair.目的　伤口愈合是细胞增生受到严密调控的过程。细胞生长取决于细胞周期正负调控因子间的相互作用及平衡。本研究通过测定伤口愈合过程中细胞周期正向调控因子CyclinD1、CyclinE、CDK2 、CDK4 及负向调控因子p2 1cip1、p2 7kip1、p16 ink4a、p15 ink4b的表达变化 ,旨在探讨愈合过程中生长调控机制及意义。方法　采用大鼠全皮层开放伤模型 ,收集伤后 3- 30日伤口组织 ,以免疫组织化学法测定Ki6 7的表达 ,Westernblot法检测CyclinD1、CyclinE、CDK2 、CDK4 及p2 1cip1、p2 7kip1、p16 ink4a、p15 ink4b。结果　细胞生长主要发生在伤后一周之内 ,生长高峰出现在伤后 5日。CyclinD1、CDK2 、CDK4 的表达均保持较为恒定的水平 ,整个愈合过程无明显的起伏变化 ;伤后 3- 11日 ,CyclinE呈高表达 ,14日开始明显下降 ,伤后 2 1-30日几乎回落到伤前水平。Westernblot法未检测到p16 ink4a、p15 ink4b的表达 ;p2 1cip1在伤后 7- 14日呈一过性表达 ,其峰值水平出现在伤后 9日 ;p2 7kip1呈结构性表达 ,伤后 3- 5日表达强度相对低下 ,随后大幅度上调。p2 1cip1、p2 7kip1表达确与Ki6 7的表达呈反向趋势。结论　伤口愈合过程中 ,p2 1cip1、p2 7kip1在防止过度增生趋势中发挥着监控作用 ,其中p2 7kip1的作用更为重要。

关 键 词：Wound Healing Animals Cell Cycle Cell Cycle Proteins Cell Division Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases CYCLINS Male RATS Rats  Wistar Research Support  Non-U.S. Gov't Skin Tumor Suppressor Proteins 

分 类 号：R602[医药卫生—外科学]