Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium
Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium
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DOI：
10.1152/ajprenal.00247.2015
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发表时间：
2015-09-15
影响因子：
4.2
通讯作者：
Mullins, John J.
中科院分区：
文献类型：
--
作者：
Rider, Sebastien A.;Mullins, Linda J.;Mullins, John J.
虽然肾素是心血管系统的关键调节酶，但它在器官发生和建立心血管内稳态中的作用尚不清楚。哺乳动物肾素表达细胞广泛存在于胚胎肾脏中，但在成人中是高度受限的特化内分泌细胞。具有功能性前肾的胚胎斑马鱼是描述肾素表达细胞的发育功能和肾素转录调控机制的理想工具。斑马鱼幼体肾素的表达起源于肾小球旁系膜前动脉的壁细胞，随后在肾外部位表达。通过评估肾素-血管紧张素系统阻断、盐度变化和肾脏灌注消融的反应来确定肾素的作用。肾素表达对肾血流消融无反应，但受血管紧张素转换酶抑制和盐度改变的调节。我们在仔鱼中的数据与肾素的生理功能保守是一致的。使用转基因肾素报告FISH，通过Mind Bomb和Cloche突变体，我们表明Notch信号和内皮细胞对于发育中的肾素表达是必不可少的。在抑制血管生成后，表达肾素的细胞先于新生血管萌发。肾素表达细胞起源于不同的谱系，但依赖于与内皮细胞的相互作用，是幼鱼中观察到的最早的壁细胞之一，具有内分泌和旁分泌功能。
Although renin is a critical regulatory enzyme of the cardiovascular system, its roles in organogenesis and the establishment of cardiovascular homeostasis remain unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but are highly restricted, specialized endocrine cells in adults. With a functional pronephros, embryonic zebrafish are ideal for delineating the developmental functions of renin-expressing cells and the mechanisms governing renin transcription. Larval zebrafish renin expression originates in the mural cells of the juxtaglomerular anterior mesenteric artery and subsequently at extrarenal sites. The role of renin was determined by assessing responses to renin-angiotensin system blockade, salinity variation, and renal perfusion ablation. Renin expression did not respond to renal flow ablation but was modulated by inhibition of angiotensin-converting enzyme and altered salinity. Our data in larval fish are consistent with conservation of renin's physiological functions. Using transgenic renin reporter fish, with mindbomb and cloche mutants, we show that Notch signaling and the endothelium are essential for developmental renin expression. After inhibition of angiogenesis, renin-expressing cells precede angiogenic sprouts. Arising from separate lineages, but relying on mutual interplay with endothelial cells, renin-expressing cells are among the earliest mural cells observed in larval fish, performing both endocrine and paracrine functions.