Induction of p53-dependent p21 limits proliferative activity of rat hepatocytes in the presence of hepatocyte growth factor.
Induction of p53-dependent p21 limits proliferative activity of rat hepatocytes in the presence of hepatocyte growth factor.
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DOI：
10.1371/journal.pone.0078346
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Koike K
中科院分区：
文献类型：
--
作者：
Inoue Y;Tomiya T;Nishikawa T;Ohtomo N;Tanoue Y;Ikeda H;Koike K
肝细胞生长因子（HGF）是一种有效的肝细胞有丝分裂原，可增强肝细胞功能而不刺激增殖，这取决于生理条件。p53是一种转录因子，通过在各种组织中表达p21 WAF 1/CIP 1来抑制细胞增殖。探讨肝细胞在HGF存在下仍保持有丝分裂静止的机制。本实验研究了肝细胞生长因子（HGF）刺激原代培养大鼠肝细胞p53和p21表达的关系及p53-p21轴对肝细胞增殖的影响。在大鼠部分肝切除术或假手术后连续测定肝脏p21水平。在低密度培养的大鼠肝细胞中，加入HGF可显著增加DNA合成，但在高密度培养时则无此作用。在两种密度下培养的肝细胞中，细胞p53水平均升高。在高密度培养的肝细胞中，p21水平升高，并与细胞p53水平相关，但在低密度培养的肝细胞中则不相关。当p53的活性被p53的化学抑制剂抑制时，细胞p21水平降低，DNA合成增加。同样，p21反义寡核苷酸增加DNA合成。在部分肝切除术后的大鼠中，观察到肝脏p21水平短暂升高。相反，在假手术大鼠中，肝脏p21水平在持续的时间尺度上增加。p53相关的p21诱导可能抑制肝细胞增殖的HGF的存在下，在设置中，促有丝分裂活性的HGF是不诱发。
Hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, enhances hepatocyte function without stimulating proliferation, depending on the physiological conditions. p53, a transcription factor, suppresses the cell proliferation by expressing p21WAF1/CIP1 in various tissues. To investigate the mechanism through which the hepatocytes maintain mitotically quiescent even in the presence of HGF. We studied the relationship between p53 and p21 expression and the effect of p53-p21 axis on hepatocyte proliferation in primary cultured rat hepatocytes stimulated by HGF. Hepatic p21 levels are determined serially after partial hepatectomy or sham operation in rats. DNA synthesis was markedly increased by HGF addition in rat hepatocytes cultured at low density but not at high density. Cellular p53 levels increased in the hepatocytes cultured at both the densities. p21 levels were increased and correlated with cellular p53 levels in hepatocytes cultured at high density but not at low density. When the activity of p53 was suppressed by a chemical inhibitor for p53, cellular p21 levels were reduced, and DNA synthesis was increased. Similarly, p21 antisense oligonucleotide increased the DNA synthesis. In rats after partial hepatectomy, transient elevation of hepatic p21 levels was observed. In contrast, in sham-operated rats, hepatic p21 levels were increased on sustained time scales. p53-related induction of p21 may suppress hepatocyte proliferation in the presence of HGF in the setting that mitogenic activity of HGF is not elicitable.
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影响因子：
10.5
作者：
LaBaer, J;Garrett, MD;Harlow, E
通讯作者：
Harlow, E
DOI：
10.1006/bbrc.1997.6938
发表时间：
1997-07-18
影响因子：
3.1
作者：
Conner, EA;Wirth, PJ;Thorgeirsson, SS
通讯作者：
Thorgeirsson, SS
影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
56.9
作者：
Chin, YE;Kitagawa, M;Fu, XY
通讯作者：
Fu, XY