Zhang Yanling, Shi Yonghong, Liu Yaling, Dong Hui, Liu Maodong, Li Ying, Duan Huijun
Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang 050051, China.
Biochem Biophys Res Commun. 2007 Nov 9;363(1):159-64. doi: 10.1016/j.bbrc.2007.08.139. Epub 2007 Aug 31.
Renal hypertrophy, partly due to cell proliferation and hypertrophy, has been found correlated to renal function deterioration in diabetes mellitus. We screened the up-regulated cell cycle related genes to investigate cell growth and the expression of cell cycle regulating proteins at the early stage of diabetic nephropathy using STZ-induced diabetic rats. Cyclin E, CDK(2) and P(27) were found significantly up-regulated in diabetic kidney. Increased cell proliferation in the kidney was seen at day 3, peaked at day 5, and returned to normal level at day 30. Cyclin E and CDK(2) expression also peeked at day 5 and P(27) activity peaked at day 14. These findings indicate that a hyperplastic growth period of renal cells is followed by a hypertrophic growth period at the early stage of diabetes. The growth pattern switch may be regulated by cell cycle regulating proteins, Cyclin E, CDK(2), and P(27).
肾肥大部分归因于细胞增殖和肥大,已发现其与糖尿病患者的肾功能恶化相关。我们使用链脲佐菌素诱导的糖尿病大鼠,筛选上调的细胞周期相关基因,以研究糖尿病肾病早期的细胞生长和细胞周期调节蛋白的表达。发现糖尿病肾脏中细胞周期蛋白E、细胞周期蛋白依赖性激酶(CDK)(2)和P(27)显著上调。肾脏细胞增殖在第3天增加,第5天达到峰值,第30天恢复到正常水平。细胞周期蛋白E和CDK(2)的表达也在第5天达到峰值,P(27)活性在第14天达到峰值。这些发现表明,在糖尿病早期,肾细胞经历了一个增生性生长阶段,随后是肥大性生长阶段。生长模式的转变可能受细胞周期调节蛋白细胞周期蛋白E、CDK(2)和P(27)的调控。