Cell cycle-mediated regulation of hepatic regeneration
Cell cycle-mediated regulation of hepatic regeneration
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DOI：
10.1016/s0039-6060(97)90334-2
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发表时间：
1997-11-01
期刊：
影响因子：
3.8
通讯作者：
Evers, BM
中科院分区：
文献类型：
--
作者：
Ehrenfried, JA;Ko, TC;Evers, BM
背景资料。肝部分切除(PH)后肝再生的特点是同时诱导正常静止的肝细胞重新进入细胞周期，导致肝脏质量完全恢复。细胞周期进程需要细胞周期蛋白依赖性蛋白激酶(CDK)的激活，该蛋白受细胞周期蛋白和细胞周期蛋白依赖性蛋白依赖性蛋白激酶抑制剂的调节。免疫印迹法检测F344大鼠假手术或PH后细胞周期蛋白(D型和E型)、CDK2和CDK4及其抑制物(p21和p27)的蛋白表达。此外，还检测了CDK2相关蛋白的活性。在大鼠PH后，D型和E型细胞周期蛋白及其催化配对CDK2和CDK4的快速诱导发生。含有细胞周期蛋白E和CDK2的复合体聚集在再生的肝脏中，导致CDK2相关的激酶活性增加。再生的肝脏在第7天恢复到切除前的重量，此时CDK2的活性也恢复到假手术水平。CDK抑制剂p21的表达呈双相诱导，第一个表达高峰出现在PH后6h，随后的表达高峰出现在PH后24~72h。综上所述，这些数据支持周期蛋白、CDK和CDK抑制剂调节再生肝细胞周期进程的观点。此外，p21在两个时间点的诱导表明，该蛋白可能调节肝细胞早期增殖和随后的肝细胞再生抑制。
Background. Hepatic regeneration after partial hepatectomy (PH) is characterized by a synchronous induction of normally quiescent hepatocytes to reenter the cell cycle, leading to a complete restoration of hepatic mass. Cell cycle progression requires activation of cyclin-dependent kinases (Cdks) that are regulated by cyclins and Cdk inhibitors.Methods. Protein expression of the cyclins (D-type and E), Cdks (Cdk2 and 4), and Cdk inhibitors (p21 and p27) was measured by Western blot after SHAM operation or PH in F344 rats. In addition, Cdk2-associated kinase activity was measured.Results. Rapid induction of D-type and E cyclins, as well as their catalytic partners, Cdk2 and Cdk4, occurred after PH in rats. Complexes containing cyclin E and Cdk2 assembled in the regenerating liver, leading to increased Cdk2-associated kinase activity. The regenerating liver returned to preresection weight by day 7, at which time the Cdk2 activity also returned to SHAM levels. Biphasic induction of the Cdk inhibitor p21 was observed; the first peak occurred as early as 6 hours after PH, with a subsequent peak in expression occurring at 24 to 72 hours after PH.Conclusions. Taken together these data support the concept that cyclins, Cdks, and Cdk inhibitors regulate cell cycle progression in the regenerating liver In addition, the induction of p21 at two time points suggests that this protein may regulate both early proliferation and subsequent inhibition of hepatocyte regeneration.