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斑马鱼、小鼠和人肾脏中粘附 GPCR Gpr126(Adgrg6)的表达谱分析。

Adhesion GPCR Gpr126 (Adgrg6) Expression Profiling in Zebrafish, Mouse, and Human Kidney.

机构信息

Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.

Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.

出版信息

Cells. 2023 Aug 2;12(15):1988. doi: 10.3390/cells12151988.

Abstract

Adhesion G protein-coupled receptors (aGPCRs) comprise the second-largest class of GPCRs, the most common target for approved pharmacological therapies. aGPCRs play an important role in development and disease and have recently been associated with the kidney. Several aGPCRs are expressed in the kidney and some aGPCRs are either required for kidney development or their expression level is altered in diseased kidneys. Yet, general aGPCR function and their physiological role in the kidney are poorly understood. Here, we characterize in detail () expression based on RNAscope technology in zebrafish, mice, and humans during kidney development in adults. expression is enriched in the epithelial linage during nephrogenesis and persists in the adult kidney in parietal epithelial cells, collecting ducts, and urothelium. Single-cell RNAseq analysis shows that expression is detected in zebrafish in a distinct ionocyte sub-population. It is co-detected selectively with , , and , known to be involved in apical acid secretion, buffering blood or intracellular pH, and to maintain high cytoplasmic Ca concentration, respectively. Furthermore, -expressing cells were enriched in the expression of potassium transporter and , which regulate the expression of a calcium sensor receptor. Notably, the expression patterns of , , and in mouse kidneys are highly similar. Collectively, our approach permits a detailed insight into the spatio-temporal expression of and provides a basis to elucidate a possible role of Gpr126 in kidney physiology.

摘要

黏附 G 蛋白偶联受体(aGPCRs)是 GPCR 中第二大的家族,是大多数已批准的药物治疗的最常见靶点。aGPCRs 在发育和疾病中发挥着重要作用,最近与肾脏有关。几种 aGPCRs 在肾脏中表达,一些 aGPCRs 是肾脏发育所必需的,或者它们在患病肾脏中的表达水平发生改变。然而,aGPCR 的一般功能及其在肾脏中的生理作用仍知之甚少。在这里,我们使用 RNAscope 技术在斑马鱼、小鼠和人类中详细描述了在肾脏发育过程中的表达情况。在肾发生期间,表达在肾脏上皮谱系中丰富,并在成年肾脏中的壁细胞、集合管和尿路上皮中持续存在。单细胞 RNAseq 分析表明,在斑马鱼中,表达被检测到在一个独特的离子细胞亚群中。它与已知参与顶端酸分泌、缓冲血液或细胞内 pH 值以及维持高细胞质 Ca 浓度的 、 和 选择性共检测。此外,表达的细胞富含表达钾转运体 和 ,它们分别调节钙传感器受体的表达。值得注意的是,小鼠肾脏中 和 的表达模式非常相似。总的来说,我们的方法允许对 的时空表达进行详细的了解,并为阐明 Gpr126 在肾脏生理学中的可能作用提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1b5/10417176/c9aa4b55c56d/cells-12-01988-g001.jpg

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