COEXISTENCE OF C/EBP-ALPHA,BETA, GROWTH-INDUCED PROTEINS AND DNA-SYNTHESIS IN HEPATOCYTES DURING LIVER-REGENERATION - IMPLICATIONS FOR MAINTENANCE OF THE DIFFERENTIATED STATE DURING LIVER GROWTH
COEXISTENCE OF C/EBP-ALPHA,BETA, GROWTH-INDUCED PROTEINS AND DNA-SYNTHESIS IN HEPATOCYTES DURING LIVER-REGENERATION - IMPLICATIONS FOR MAINTENANCE OF THE DIFFERENTIATED STATE DURING LIVER GROWTH
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DOI：
10.1172/jci118170
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发表时间：
1995-09-01
影响因子：
15.9
通讯作者：
TAUB, R
中科院分区：
文献类型：
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作者：
GREENBAUM, LE;CRESSMAN, DE;TAUB, R
在三分之二部分肝切除术后的快速细胞生长期间，肝脏能够补偿其质量的三分之二的急性损失，以维持血清葡萄糖水平和其许多分化特异性功能。然而，对于分化状态的建立和维持重要的某些肝转录因子C/EBP α和β，为了研究肝细胞增殖的肝再生模型中分化和细胞生长之间的相互作用，我们表征了在整个肝再生的时间过程中C/EBP α和β转录因子的表达，如通过免疫印迹所测定的，C/EBP α水平在G1期和S期的中晚期降低两倍以上（肝切除术后8-24小时）与C/EBP β表达的三倍增加相协调，这些蛋白质水平的重新正常化发生在主要增殖期后，C/EBP α和β的这种反向调节导致β/EBP α和β的增加高达7倍。肝切除术后3至24小时的α DNA结合率可能对靶基因调控产生重要影响，然而，在肝切除术后7天期间，核提取物中的总C/EBP结合活性保持相对恒定。通过免疫组织化学，C/EBP α和β在肝再生的时间过程中几乎在整个肝的所有肝细胞核中表达，并且不排除来自表达即刻早期基因产物或经历DNA合成的肝细胞的表达，C/EBP α和β亚型的持续表达预示着C/EBP蛋白在生理生长过程中有助于肝细胞的功能，并且大量的这些蛋白不会抑制肝细胞进入细胞周期的S期。
During the period of rapid cell growth which follows a two-thirds partial hepatectomy, the liver is able to compensate for the acute loss of two-thirds of its mass to maintain serum glucose levels and many of its differentiation-specific functions, However certain hepatic transcription factors, C/EBP alpha and beta, which are important for establishment and maintenance of the differentiated state, have been shown to be antagonistic to cellular proliferation, To study the interplay between differentiation and cell growth in the liver regeneration model of hepatocyte proliferation, we characterized the expression of C/EBP alpha and beta transcription factors throughout the temporal course of liver regeneration, As determined by immunoblot, the level of C/EBP alpha decreases more than twofold during the mid to late G1 and S phase (8-24 h after hepatectomy) coordinately with a threefold increase in expression of C/EBP beta, Renormalization of the levels of these proteins occurs after the major proliferative phase, This inverse regulation of C/EBP alpha and beta results in up to a sevenfold increase in the beta/alpha DNA binding ratio between 3 and 24 h after hepatectomy that may have an important impact on target gene regulation, However, total C/EBP binding activity in nuclear extracts remains relatively constant during the 7-d period after hepatectomy, By immunohistochemistry, both C/EBP alpha and beta are expressed in virtually all hepatocyte nuclei throughout the liver during the temporal course of liver regeneration, and there is no exclusion of expression from hepatocytes that are expressing immediate-early gene products or undergoing DNA synthesis, The persistent expression of C/EBP alpha and beta isoforms predicts that C/EBP proteins contribute to the function of hepatocytes during physiologic growth and that significant amounts of these proteins do not inhibit progression of hepatocytes into S phase of the cell cycle.