INDUCTION OF P21 AND P27 IN LIVER AFTER CCL4 INJURY

描述：四氯化碳(CCl4)引起肝脏损伤，涉及 许多病理过程。对损伤的反应，肝脏有独特的 再生能力。调节肝脏再生的信号必须包括 当肝脏质量恢复时抑制细胞分裂的因素。骑自行车 蛋白激酶抑制物(CKI)p21和p27是细胞周期蛋白依赖性的有效抑制剂 激酶及其过度表达可抑制细胞周期进程。Dr。 泰纳的初步数据表明，p21和p27是不同的 在CCl4处理后在肝脏中进行调节。这两个因素的表达都是 首先定位于随着CCl4代谢而死亡的肝细胞。在… 随后的时间点，p21和p27在门静脉周围特异表达 复制以恢复肝脏质量的肝细胞。泰纳博士假设 P21和p27在G1早期的局部表达可能代表 防止受损细胞复制的检查点，以及两个CKI 在以后的时间点上调节肝脏生长的程度。P21和p27都有 据报道，它在调节细胞凋亡方面发挥作用，而且有可能 这些CKI的局部诱导也将影响细胞死亡的机制。 P21和p27在人类癌症和缺乏症中的表达降低 这些关键的细胞周期检查点蛋白可能会导致 肝损伤后易发生肝肿瘤。这些 假说将通过检查野生型的再生和细胞死亡来检验 和CKI基因敲除小鼠。P21基因对广泛的 细胞外信号及其在中心周围肝细胞中的表达 在注射CCl4后的短时间内。确定责任因素 诱导p21基因表达以响应CCl4，将导致进一步 对肝毒素启动的细胞信号级联的洞察。

DESCRIPTION: Carbon tetrachloride (CCl4) induces liver injury, which involves many pathological processes. In response to injury, the liver has the unique ability to regenerate. Signals that regulate liver regeneration must include factors that inhibit cell division when liver mass is restored. The cyclin kinase inhibitors (CKIs) p21 and p27 are potent inhibitors of cyclin dependent kinases, and their overexpression can inhibit cell cycle progression. Dr. Tyner's preliminary data indicate that both p21 and p27 are differentially regulated in the liver following CCl4 treatment. Expression of both factors is first localized to hepatocytes that will die following metabolism of CCl4. At later time points, p21 and p27 are expressed specifically in periportal hepatocytes that have replicated to restore liver mass. Dr. Tyner hypothesizes that localized expression of p21 and p27 during early G1 may represent a checkpoint that prevents damaged cells from replicating and that the two CKIs regulate the extent of liver growth at later time points. Both p21 and p27 have been reported to play roles in regulating apoptosis, and it is possible that localized induction of these CKIs will also influence mechanisms of cell death. Decreased expression of p21 and p27 has been detected in human cancers and lack of these critical cell cycle checkpoint proteins may lead to increased susceptibility to development of liver tumors following liver injury. These hypotheses will be tested by examining regeneration and cell death in wildtype and CKI knockout mice. The p21 gene is responsive to a wide array of extracellular signals and its expression is induced in pericentral hepatocytes a short time following administration of CCl4. Identifying factors responsible for inducing p21 gene expression in response to CCl4, will lead to further insight about cellular signaling cascades initiated by hepatotoxins.