Shiojiri N, Wada J I, Tanaka T, Noguchi M, Ito M, Gebhardt R
Department of Biology, Faculty of Science, Shizuoka University, Japan.
Lab Invest. 1995 Jun;72(6):740-7.
Glutamine synthetase is exclusively expressed in pericentral hepatocytes in mammalian liver, but its regulation mechanism is still largely unknown.
Heterogeneous expression of glutamine synthetase was examined in detail during mouse liver development by immunohistochemistry and by in situ hybridization. Heterogeneous expression of this enzyme was also analyzed in immature liver fragments transplanted to an ectopic site where no portal blood flow exists.
At 18.5 days of gestation, a random, spotty distribution of low levels of glutamine synthetase mRNA was observed all over the liver parenchyma, but the enzyme protein was not detectable immunohistochemically in the liver at any fetal stage. Glutamine synthetase and its mRNA began to be heterogeneously expressed in pericentral hepatocytes 2 to 3 days after birth, when glycogen accumulation in the liver parenchyma was rather homogeneous. In the early postnatal development, a mosaic distribution of positive and negative hepatocytes with respect to glutamine synthetase protein and mRNA was noted around the central veins. Subsequently, mRNA distribution gradually became continuous, although some hepatocytes still lacked protein, indicating partial regulation at the translational level. When fetal liver fragments that had not yet heterogeneously expressed glutamine synthetase were cultured under the testis capsule of male mice, only pericentral hepatocytes expressed this enzyme after 2 months. However, the distribution of glutamine synthetase protein- and mRNA-positive hepatocytes around the central veins was patchy rather than continuous, as in perinatal livers.
These results support the importance of local interactions of hepatocytes with intrahepatic cell populations and/or structural elements. Furthermore, they demonstrate that the capacity for the positional expression of glutamine synthetase is already established at a fetal age before expression of glutamine synthetase can be detected.
谷氨酰胺合成酶仅在哺乳动物肝脏的中央周围肝细胞中表达，但其调控机制仍 largely 未知。
通过免疫组织化学和原位杂交详细检测了谷氨酰胺合成酶在小鼠肝脏发育过程中的异质性表达。还分析了移植到无门静脉血流的异位部位的未成熟肝片段中该酶的异质性表达。
在妊娠 18.5 天时，在整个肝实质中观察到低水平谷氨酰胺合成酶 mRNA 的随机、斑点状分布，但在任何胎儿阶段的肝脏中均未通过免疫组织化学检测到该酶蛋白。出生后 2 至 3 天，谷氨酰胺合成酶及其 mRNA 开始在中央周围肝细胞中异质性表达，此时肝实质中的糖原积累相当均匀。在出生后早期发育阶段，围绕中央静脉观察到谷氨酰胺合成酶蛋白和 mRNA 阳性和阴性肝细胞的镶嵌分布。随后，mRNA 分布逐渐变得连续，尽管一些肝细胞仍然缺乏蛋白，表明在翻译水平存在部分调控。当尚未异质性表达谷氨酰胺合成酶的胎儿肝片段在雄性小鼠的睾丸囊中培养时，2 个月后只有中央周围肝细胞表达该酶。然而，与围产期肝脏不同，中央静脉周围谷氨酰胺合成酶蛋白和 mRNA 阳性肝细胞的分布是斑片状而非连续的。
这些结果支持肝细胞与肝内细胞群体和/或结构元件局部相互作用的重要性。此外，它们表明在可检测到谷氨酰胺合成酶表达之前的胎儿期就已经建立了谷氨酰胺合成酶位置表达的能力。
