Stromal prorenin receptor is critical for normal kidney development.
Stromal prorenin receptor is critical for normal kidney development.
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基质肾素原受体对于正常肾脏发育至关重要。
DOI：
10.1152/ajpregu.00320.2018
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
DeGoesMartini,Alexandre
中科院分区：
文献类型：
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作者：
Yosypiv,IhorV;Sequeira-Lopez,MariaLuisaS;Song,Renfang;DeGoesMartini,Alexandre
后肾的形成需要间质、输尿管芽和帽间充质之间协调的相互作用。转录因子Foxd 1是肾间质细胞的特异性标志物，对正常肾脏发育至关重要。原肾素受体（PRR）是一种肾素和原肾素的受体，也是液泡质子泵V-ATP酶的辅助亚基。PRR的整体损失在小鼠中是胚胎致死的，表明PRR在胚胎发育中的重要作用。在这里，我们报告了小鼠Foxd 1+基质祖细胞（cKO）中PRR的条件性缺失会导致新生儿死亡。存活小鼠的肾脏显示基质标志物Foxd 1和Meis 1的表达减少，动脉和小动脉发育显著减少，随后肾小球数量减少，Six 2+肾单位祖细胞扩增，肾单位分化延迟。inKO小鼠肾内动脉和小动脉更少，更薄，并表现出显着减少，在表达的肾素，提示在发展中的核心作用的PRR的肾素表达细胞，这反过来又是必要的肾动脉树的正确形成。我们的结论是，基质PRR是至关重要的肾动脉树的适当分化，这反过来可能会限制过度扩张的肾单位祖细胞，以促进协调和适当的形态发生的哺乳动物肾脏的肾血管结构。
Formation of the metanephric kidney requires coordinated interaction among the stroma, ureteric bud, and cap mesenchyme. The transcription factor Foxd1, a specific marker of renal stromal cells, is critical for normal kidney development. The prorenin receptor (PRR), a receptor for renin and prorenin, is also an accessory subunit of the vacuolar proton pump V-ATPase. Global loss of PRR is embryonically lethal in mice, indicating an essential role of the PRR in embryonic development. Here, we report that conditional deletion of thePRRin Foxd1+stromal progenitors in mice (cKO) results in neonatal mortality. The kidneys of surviving mice show reduced expression of stromal markers Foxd1 and Meis1 and a marked decrease in arterial and arteriolar development with the subsequent decreased number of glomeruli, expansion of Six2+nephron progenitors, and delay in nephron differentiation. Intrarenal arteries and arterioles incKOmice were fewer and thinner and showed a marked decrease in the expression of renin, suggesting a central role for the PRR in the development of renin-expressing cells, which in turn are essential for the proper formation of the renal arterial tree. We conclude that stromal PRR is crucial for the appropriate differentiation of the renal arterial tree, which in turn may restrict excessive expansion of nephron progenitors to promote a coordinated and proper morphogenesis of the nephrovascular structures of the mammalian kidney.