The structural-functional organization of ammonia and glutamine metabolism in the liver acinus involves highly specialized hepatocyte subpopulations like glutamine synthetase (GS) expressing perivenous hepatocytes (scavenger cells). However, this cell population has not yet been characterized extensively regarding expression of other genes and potential subpopulations. This was investigated in the present study by proteome profiling of periportal GS-negative and perivenous GS-expressing hepatocytes from mouse and rat. Apart from established markers of GS+ hepatocytes such as glutamate/aspartate transporter II (GLT1) or ammonium transporter Rh type B (RhBG), we identified novel scavenger cell-specific proteins like basal transcription factor 3 (BTF3) and heat-shock protein 25 (HSP25). Interestingly, BTF3 and HSP25 were heterogeneously distributed among GS+ hepatocytes in mouse liver slices. Feeding experiments showed that RhBG expression was increased in livers from mice fed with high protein diet compared to standard chow. While spatial distributions of GS and carbamoylphosphate synthetase 1 (CPS1) were unaffected, periportal areas constituted by glutaminase 2 (GLS2)-positive hepatocytes were enlarged or reduced in response to high or low protein diet, respectively. The data suggest that the population of perivenous GS+ scavenger cells is heterogeneous and not uniform as previously suggested which may reflect a functional heterogeneity, possibly relevant for liver regeneration.

中文翻译：

---

小鼠和大鼠肝脏中清道夫细胞蛋白质组的表征


肝腺泡中氨和谷氨酰胺代谢的结构功能组织涉及高度特化的肝细胞亚群，例如表达谷氨酰胺合成酶（GS）的静脉周围肝细胞（清道夫细胞）。然而，该细胞群尚未在其他基因和潜在亚群的表达方面得到广泛表征。本研究通过对小鼠和大鼠的门静脉周围 GS 阴性和静脉周围 GS 表达肝细胞的蛋白质组分析进行了研究。除了已建立的 GS+ 肝细胞标记物（如谷氨酸/天冬氨酸转运蛋白 II (GLT1) 或铵转运蛋白 Rh 型 B (RhBG)）外，我们还鉴定了新型清道夫细胞特异性蛋白，如基础转录因子 3 (BTF3) 和热休克蛋白 25（热休克蛋白25）。有趣的是，BTF3 和 HSP25 在小鼠肝脏切片中的 GS+ 肝细胞中分布不均匀。喂养实验表明，与标准饲料相比，高蛋白饮食喂养的小鼠肝脏中 RhBG 表达增加。虽然 GS 和氨基甲酰磷酸合成酶 1 (CPS1) 的空间分布不受影响，但由谷氨酰胺酶 2 (GLS2) 阳性肝细胞构成的门静脉周围区域分别因高蛋白饮食或低蛋白饮食而增大或减小。数据表明，静脉周围 GS+ 清道夫细胞群是异质的，并不像之前所建议的那样均匀，这可能反映了功能异质性，可能与肝再生有关。