COEXPRESSION OF LIVER-SPECIFIC AND GROWTH-INDUCED GENES IN PERINATAL AND REGENERATING LIVER - ATTAINMENT AND MAINTENANCE OF THE DIFFERENTIATED STATE DURING RAPID PROLIFERATION
COEXPRESSION OF LIVER-SPECIFIC AND GROWTH-INDUCED GENES IN PERINATAL AND REGENERATING LIVER - ATTAINMENT AND MAINTENANCE OF THE DIFFERENTIATED STATE DURING RAPID PROLIFERATION
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DOI：
10.1002/hep.1840220331
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发表时间：
1995-09-01
期刊：
影响因子：
13.5
通讯作者：
TAUB, R
中科院分区：
文献类型：
--
作者：
HABER, B;NAJI, L;TAUB, R
在胎儿发育期间和部分肝切除术后，肝脏显示出最大的细胞生长。探索这两种类型的肝脏生长中基因表达模式的重叠可能会提供对共同调控途径的见解。从出生前几天到出生后4周，当肝脏的主要生长阶段停止时，在围产期肝脏中检查了大量生长诱导和肝脏特异性基因在肝脏再生中诱导的表达。在肝再生中，许多生长诱导基因，如PRL-1和β-肌动蛋白，在整个肝脏发育的时间过程中以高水平表达，并与增殖状态相关。这些基因的胎肝表达水平与再生肝中发现的峰值表达相似，表明两种增殖类型中存在共同的转录调控途径。肝脏限制性立即早期基因的一个子集，包括IGFBP-1，CL-6和葡萄糖-6-磷酸酶（G6 β）在再生肝脏中被诱导，并可能在再生过程中维持肝脏代谢中起重要作用。在发育中的肝脏中，这些基因主要在围产期表达，但与再生肝脏不同，它们不是共同诱导的。例如，在出生时，G6 β被诱导，而CL-6被下调。原位分析证实，增殖相关基因PRL-1在整个发育中的肝脏中的多种细胞类型中表达，而肝脏特异性基因的表达仅限于肝细胞。综上所述，这些研究结果表明，显着的相似性和差异的转录调控和激素环境中存在的肝脏再生和发展。在肝脏的增殖状态中，负责葡萄糖稳态的基因表达增加，表明维持分化功能是肝脏生长反应的一个组成部分。
The liver shows maximal cellular growth during fetal development and after partial hepatectomy. Exploring overlaps in gene expression patterns in these two types of hepatic growth may provide insight into common regulatory pathways. The expression of a large number of growth-induced and liver-specific genes induced in liver regeneration has been examined in the perinatal liver from several days prenatal to 4 weeks postnatal when the major growth phase of the liver ceases. As in liver regeneration, many growth-induced genes, such as PRL-1 and beta-actin, are expressed at a high level throughout the temporal course of liver development and correlate with the proliferative state. The level of fetal liver expression of these genes is similar to peak expression found in the regenerating liver, suggesting that common pathways of transcriptional regulation exist in the two types of proliferation. A subset of liver-restricted immediate-early genes including, IGFBP-1, CL-6, and glucose-6-phosphatase (G6Pase) are induced in regenerating liver and may be important in maintaining hepatic metabolism during regeneration. In developing liver, these genes are expressed primarily in the perinatal period but, unlike the regenerating liver, are not coinduced. For instance, at birth, G6Pase is induced, whereas CL-6 is downregulated. In situ analyses confirm that a proliferation associated gene PRL-1 is expressed in multiple cell types throughout the developing liver, whereas the expression of liver-specific genes is confined to hepatocytes. Taken together, these findings imply that significant similarities and differences in transcriptional regulation and hormonal milieu exist in liver during regeneration and development. The increased expression of genes responsible for glucose homeostasis in proliferative states of the liver suggests that maintenance of differentiated function is a component of the hepatic growth response.