Identification and developmental analysis of endothelin receptor type-A expressing cells in the mouse kidney

Identification and developmental analysis of endothelin receptor type-A expressing cells in the mouse kidney
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DOI:
10.1016/j.gep.2011.04.001
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发表时间:
2011-10-01
影响因子:
1.2
通讯作者:
Kurihara, Hiroki
Kurihara, Hiroki
中科院分区:
生物学4区
文献类型:
--
作者:
Kitazawa, Taro;Sato, Takahiro;Kurihara, Hiroki

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内皮素(EDN)系统通过两种不同的G蛋白偶联受体-A型EDN受体(EDNRA)和B型受体(EDNRB)在肾功能和各种疾病过程中发挥多向作用。然而,在原位准确识别受体表达细胞的困难使得很难剖析它们在肾脏(病理)生理中的不同作用。我们最近建立了LacZ和EGFP‘敲入’Ednra基因的小鼠系,以忠实地标记Ednra表达细胞。在这里,我们分析了这些小鼠在肾脏中的表达,以确定表达Ednra的细胞的特征。首次在胚胎12.5的输尿管芽周围的未分化间充质细胞中观察到Ednra的表达。此后,Ednra广泛表达于间质中的血管平滑肌细胞、JG细胞和间充质细胞。生长后,该基因的表达仅限于血管平滑肌细胞、周细胞和产生肾素的JG细胞。相反,肾单位和血管内皮细胞中的大多数细胞不表达Ednra。这些结果表明,Ednra的表达可能与后肾间充质的分化和非上皮性命运的决定有关。Ednra-LacZ/EGFP敲入小鼠可作为研究肾功能和各种肾脏疾病病理生理学的有用工具。(C)2011爱思唯尔B.V.保留所有权利。
The endothelin (Edn) system plays pleiotropic roles in renal function and various disease processes through two distinct G protein-coupled receptors, Edn receptors type-A (Ednra) and type-B (Ednrb). However, difficulties in the accurate identification of receptor-expressing cells in situ have made it difficult to dissect their diverse action in renal (patho)physiology. We have recently established mouse lines in which lacZ and EGFP are 'knocked-in' to the Ednra locus to faithfully mark Ednra-expressing cells. Here we analyzed these mice for their expression in the kidney to characterize Ednra-expressing cells. Ednra expression was first observed in undifferentiated mesenchymal cells around the ureteric bud at E12.5. Thereafter, Ednra expression was widely observed in vascular smooth muscle cells, JG cells and mesenchymal cells in the interstitium. After growth, the expression became confined to vascular smooth muscle cells, pericytes and renin-producing JG cells. By contrast, most cells in the nephron and vascular endothelial cells did not express Ednra. These results indicate that Ednra expression may be linked with non-epithelial fate determination and differentiation of metanephric mesenchyme. Ednra-lacZ/EGFP knock-in mice may serve as a useful tool in studies on renal function and pathophysiology of various renal diseases. (C) 2011 Elsevier B.V. All rights reserved.