Paluschinski Martha, Jin Cheng Jun, Qvartskhava Natalia, Görg Boris, Wammers Marianne, Lang Judith, Lang Karl, Poschmann Gereon, Stühler Kai, Häussinger Dieter
Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Biol Chem. 2021 Jul 30;402(9):1073-1085. doi: 10.1515/hsz-2021-0123. Print 2021 Aug 26.
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.
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，如表达谷氨酰胺合成酶（GS）的终末肝静脉周围肝细胞（清除细胞）。然而，关于该细胞群体的其他基因表达和潜在亚群尚未进行广泛的表征。本研究通过对来自小鼠和大鼠的门静脉周围GS阴性和终末肝静脉周围GS阳性肝细胞进行蛋白质组分析来对此进行研究。除了已确定的GS肝细胞标志物，如谷氨酸/天冬氨酸转运体II（GLT1）或B型Rh铵转运体（RhBG）外，我们还鉴定了新的清除细胞特异性蛋白，如基础转录因子3（BTF3）和热休克蛋白25（HSP25）。有趣的是，BTF3和HSP25在小鼠肝切片的GS肝细胞中呈异质性分布。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）的空间分布未受影响，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或低蛋白饮食而扩大或缩小。数据表明，终末肝静脉周围GS清除细胞群体是异质性的，并非如先前认为的那样均匀，这可能反映了功能异质性，可能与肝再生有关。
