Schulze Blasum Britta, Schröter Rita, Neugebauer Ute, Hofschröer Verena, Pavenstädt Hermann, Ciarimboli Guiliano, Schlatter Eberhard, Edemir Bayram
Department of Internal Medicine D, Experimental Nephrology, University of Münster, Münster, Germany.
Institute of Physiology II, University of Münster, Münster, Germany; and.
FASEB J. 2016 Oct;30(10):3588-3597. doi: 10.1096/fj.201600319R. Epub 2016 Jul 27.
With this study, we wanted to prove the hypothesis that the unique extracellular osmolality within the renal medulla modulates a specific gene expression pattern. The physiologic functions of the kidneys are mediated by the segment-specific expression of key proteins. So far, we have limited knowledge about the mechanisms that control this gene expression pattern. The hyperosmolality in the renal medullary interstitium is of major importance as a driving force for urine concentration. We made use of primarily cultured rat renal inner medullary collecting-duct cells and microarray analysis to identify genes affected by the environmental osmolality of the culture medium. We identified hundreds of genes that were either induced or repressed in expression by hyperosmolality in a time- and osmolality-dependent fashion. Further analysis demonstrated that many of them, physiologically, showed a kidney- and even collecting-duct-specific expression, including secreted proteins, kinases, and transcription factors. On the other hand, we identified factors, down-regulated in expression, that have a diuretic effect. In conclusion, the kidney is the only organ that has such a hyperosmotic environment, and study provides an excellent method for controlling tissue-specific gene expression.-Schulze Blasum, B., Schröter, R., Neugebauer, U., Hofschröer, V., Pavenstädt, H., Ciarimboli, G., Schlatter E., Edemir, B. The kidney-specific expression of genes can be modulated by the extracellular osmolality.
通过这项研究,我们想要证实这样一个假设,即肾髓质内独特的细胞外渗透压调节特定的基因表达模式。肾脏的生理功能由关键蛋白的节段特异性表达介导。到目前为止,我们对控制这种基因表达模式的机制了解有限。肾髓质间质中的高渗作为尿液浓缩的驱动力至关重要。我们利用原代培养的大鼠肾内髓集合管细胞和微阵列分析来鉴定受培养基环境渗透压影响的基因。我们鉴定出数百个基因,其表达在高渗作用下呈时间和渗透压依赖性地被诱导或抑制。进一步分析表明,其中许多基因在生理上表现出肾脏甚至集合管特异性表达,包括分泌蛋白、激酶和转录因子。另一方面,我们鉴定出表达下调且具有利尿作用的因子。总之,肾脏是唯一具有这种高渗环境的器官,本研究提供了一种控制组织特异性基因表达的优秀方法。——舒尔茨·布拉苏姆,B.,施罗特,R.,诺伊格鲍尔,U.,霍夫施勒尔,V.,帕文施泰特,H.,西亚林博利,G.,施拉特,E.,埃德米尔,B. 基因的肾脏特异性表达可由细胞外渗透压调节。