O'Carroll Anne-Marie, Salih Sabrine, Griffiths Philip R, Bijabhai Aarifah, Knepper Mark A, Lolait Stephen J
Bristol Medical School, HW-LINE, University of Bristol, Bristol, United Kingdom.
Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS One. 2017 Aug 17;12(8):e0183094. doi: 10.1371/journal.pone.0183094. eCollection 2017.
Apelin binds to the G protein-coupled apelin receptor (APJ; gene name aplnr) to modulate diverse physiological systems including cardiovascular function, and hydromineral and metabolic balance. Recently a second endogenous ligand for APJ, named apela, has been discovered. We confirm that apela activates signal transduction pathways (ERK activation) in cells expressing the cloned rat APJ. Previous studies suggest that exogenous apela is diuretic, attributable wholly or in part to an action on renal APJ. Thus far the cellular distribution of apela in the kidney has not been reported. We have utilized in situ hybridization histochemistry to reveal strong apela labelling in the inner medulla (IM), with lower levels observed in the inner stripe of the outer medulla (ISOM), of rat and mouse kidneys. This contrasts with renal aplnr expression where the converse is apparent, with intense labelling in the ISOM (consistent with vasa recta labelling) and low-moderate hybridization in the IM, in addition to labelling of glomeruli. Apelin is found in sparsely distributed cells amongst more prevalent aplnr-labelled cells in extra-tubular regions of the medulla. This expression profile is supported by RNA-Seq data that shows that apela, but not apelin or aplnr, is highly expressed in microdissected rat kidney tubules. If endogenous tubular apela promotes diuresis in the kidney it could conceivably do this by interacting with APJ in vasculature, or via an unknown receptor in the tubules. The comparative distribution of apela, apelin and aplnr in the rodent kidney lays the foundation for future work on how the renal apelinergic system interacts.
阿片肽与G蛋白偶联的阿片肽受体（APJ；基因名称aplnr）结合，以调节包括心血管功能、水盐和代谢平衡在内的多种生理系统。最近，已发现APJ的第二种内源性配体，名为阿片肽原（apela）。我们证实，阿片肽原可激活表达克隆大鼠APJ的细胞中的信号转导通路（ERK激活）。先前的研究表明，外源性阿片肽原具有利尿作用，这完全或部分归因于其对肾脏APJ的作用。迄今为止，尚未报道阿片肽原在肾脏中的细胞分布情况。我们利用原位杂交组织化学技术揭示，在大鼠和小鼠肾脏的内髓质（IM）中阿片肽原有强烈的标记，在外髓质内带（ISOM）中观察到的水平较低。这与肾脏aplnr的表达形成对比，后者情况相反，ISOM中有强烈标记（与直小血管标记一致），IM中有低至中等程度的杂交信号，此外肾小球也有标记。在髓质的肾小管外区域，阿片肽存在于分布稀疏的细胞中，周围是更普遍的aplnr标记细胞。RNA测序数据支持了这种表达模式，该数据表明，阿片肽原在显微解剖的大鼠肾小管中高表达，而阿片肽或aplnr则不然。如果内源性肾小管阿片肽原在肾脏中促进利尿，那么可以想象它可能通过与血管系统中的APJ相互作用，或者通过肾小管中的未知受体来实现。阿片肽原、阿片肽和aplnr在啮齿动物肾脏中的比较分布为未来研究肾脏阿片肽能系统如何相互作用奠定了基础。
