Timing of hepatocyte entry into DNA synthesis after partial hepatectomy is cell autonomous.
Timing of hepatocyte entry into DNA synthesis after partial hepatectomy is cell autonomous.
复制标题
DOI：
10.1073/pnas.220430497
复制
发表时间：
2000-11
影响因子：
11.1
通讯作者：
T. C. Weglarz;E. Sandgren
中科院分区：
文献类型：
--
作者：
T. C. Weglarz;E. Sandgren
手术切除三分之二的肝脏后，剩余的肝细胞在2周内复制并恢复肝脏肿块。这一过程必须由肝细胞的外部信号启动，但尚不清楚导致DNA合成的后续事件（S期）是由循环或局部产生的生长因子（非细胞自主反应）调节的，还是由肝细胞本身固有的程序（细胞自主反应）调节的。为了确定向S传递的调节机制类型，我们利用了大鼠和小鼠肝细胞在部分肝切除术后DNA合成时间的差异，与小鼠相比，大鼠在肝切除术后12-16小时达到峰值。四组动物接受了三分之二的部分肝切除术：大鼠、小鼠、由移植的大鼠肝细胞和内源性小鼠肝细胞组成的嵌合肝脏小鼠，以及由移植的和内源性小鼠肝细胞组成的嵌合肝脏小鼠。在三分之二的部分肝切除术后，小鼠/小鼠嵌合肝脏中的供体和内源性肝细胞都显示出小鼠DNA合成特征的动力学，这表明移植本身并不影响对随后的部分肝切除术的反应。相比之下，嵌合小鼠肝脏中的大鼠肝细胞尽管存在于小鼠宿主中，但仍表现出大鼠动力学。因此，肝细胞的内在因子必须调节进入DNA合成的时间。这一结果将这一过程定义为细胞自主的，并表明局部或远处产生的细胞因子或生长因子可能在S的进展中起许可作用，而不是指导作用。
After surgical removal of two-thirds of the liver, remaining hepatocytes replicate and restore hepatic mass within 2 weeks. This process must be initiated by signals extrinsic to the hepatocyte, but it remains unclear whether subsequent events leading to DNA synthesis (S phase) are regulated by circulating or locally produced growth factors (a noncell autonomous response), or by a program intrinsic to the hepatocyte itself (a cell autonomous response). To identify the type of mechanism regulating passage to S, we exploited the difference between rat and mouse hepatocytes in the timing of DNA synthesis after partial hepatectomy, which peaks 12-16 h earlier posthepatectomy in rat compared with mouse. Four groups of animals received two-thirds partial hepatectomies: rats, mice, mice with chimeric livers composed of both transplanted rat hepatocytes and endogenous mouse hepatocytes, and mice with chimeric livers composed of both transplanted and endogenous mouse hepatocytes. Following two-thirds partial hepatectomy, both donor and endogenous hepatocytes in mouse/mouse chimeric livers displayed kinetics of DNA synthesis characteristic of the mouse, indicating that transplantation per se did not affect the response to subsequent partial hepatectomy. In contrast, rat hepatocytes in chimeric mouse livers displayed rat kinetics despite their presence in a mouse host. Thus, factors intrinsic to the hepatocyte must regulate the timing of entry into DNA synthesis. This result defines the process as cell autonomous and suggests that locally or distantly produced cytokines or growth factors may have a permissive but not an instructive role in progression to S.