Experimental evidence that the physiological position of the liver within the circulation is not a major determinant of zonation of gene expression-猫眼课题宝

实验证据表明肝脏在循环中的生理位置并不是基因表达分区的主要决定因素

DOI：

发表时间：

1993

期刊：

Hepatology

影响因子：

13.5

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

G. Wagenaar;R. Chamuleau;J. de Haan;M. Maas;P. D. de Boer;F. Marx;A. Moorman;W. Frederiks;W. Lamers

许多酶在肝小叶内分布不均。在这些异质表达模式的建立和维持中起决定性作用的因素尚未确定。为了研究肝传入血的成分是否在维持肝小叶内实质细胞基因表达异质性中起关键作用，我们通过显微外科技术改变了肝传入血的来源。研究了三组不同的实验动物：肝脏只灌注门静脉血（肝动脉结扎）、只灌注腔血（门静脉转位和肝动脉结扎）和只灌注动脉血（门静脉分流、门静脉远端动脉化和肝动脉结扎）的大鼠。为了研究基因表达模式的差异，我们选择了肝小叶内具有异质表达模式的酶：位于肝小叶周围的酶：氨甲酰磷酸合成酶、琥珀酸脱氢酶、磷酸烯醇丙酮酸羧激酶和位于肝小叶周围的酶：谷氨酰胺合成酶、谷氨酸脱氢酶和nadph -细胞色素P‐450还原酶。为了消除其中一些蛋白质的长半衰期对结果解释的潜在干扰，我们还研究了氨甲酰磷酸合酶、谷氨酰胺合酶、谷氨酸脱氢酶和磷酸烯醇丙酮酸羧激酶mrna的分布。术后2周对动物进行研究。根据体重的变化，这些动物至少在一周内处于稳定状态。研究的酶的基因表达模式没有改变，不管改变的传入肝血的来源。在没有恢复术前体重的动物身上观察到的基因表达变化被证明是由有限的食物摄入引起的。这项研究表明，肝脏在循环中的生理位置（即在胃肠道和体循环之间）并不像通常所说的那样重要，当然也不是维持肝细胞异质性的必要条件。数据表明，血流的方向（即上游和下游室的存在）是基因表达分区的主要决定因素。(肝脏病学1993;18:1144量1153)。

Many enzymes are distributed heterogeneously within the liver lobule. The factors that play a determining role in the establishment and maintenance of these heterogeneous expression patterns have not yet been identified. To investigate whether the composition of the afferent hepatic blood plays a crucial role in the maintenance of the heterogeneity of gene expression of the parenchymal cells within the liver lobule, we changed the source of the afferent hepatic blood by microsurgical techniques. Three different groups of experimental animals were studied: rats with livers that are perfused with portal blood only (ligation of the hepatic artery), with caval blood only (portocaval transposition and ligation of the hepatic artery) and arterial blood only (portocaval shunt, arterialization of the distal end of the portal vein and ligation of the hepatic artery). To study differences in gene expression patterns, we chose enzymes that have a heterogeneous expression pattern within the liver lobule: the periportally located enzymes carbamoylphosphate synthase, succinate dehydrogenase, phosphoenolpyruvate carboxylkinase and the pericentrally located enzymes glutamine synthase, glutamate dehydrogenase and NADPH–cytochrome P‐450 reductase. To eliminate the potential interference of the long half‐lives of some of these proteins on the interpretation of the results, we also studied the distribution of the mRNAs of carbamoylphosphate synthase, glutamine synthase, glutamate dehydrogenase and phosphoenolpyruvate carboxykinase. The animals were studied 2 wk after the operations. On the basis of their changes in body weight the animals were in steady state for at least a week. The patterns of gene expression of the enzymes studied did not change, regardless of the source of the altered afferent hepatic blood. The changes in gene expression that were observed in animals that did not regain their preoperative weight were shown to be caused by a limited intake of food. This study demonstrates that the physiological position of the liver within the circulation (i.e., between the gastrointestinal tract and the systemic circulation) is not as critical as is often stated and is certainly not essential for the maintenance of liver cell heterogeneity. The data suggest that the direction of the bloodstream (i.e., the existence of an upstream and a downstream compartment) is a major determinant of zonation of gene expression. (HEPATOLOGY 1993;18:1144‐1153).

Isolation and characterization of the gene coding for cytosolic phosphoenolpyruvate carboxykinase (GTP) from the rat.