The cytoplasmic protein Pacsin 2 in kidney development and injury repair
The cytoplasmic protein Pacsin 2 in kidney development and injury repair
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DOI：
10.1038/ki.2012.379
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发表时间：
2013-03-01
影响因子：
19.6
通讯作者：
Zhou, Jing
中科院分区：
文献类型：
--
作者：
Yao, Gang;Luyten, Annouck;Zhou, Jing
神经元中的蛋白激酶C和酪蛋白激酶2底物(Pacsin)是膜结合蛋白的一个亚家族，参与囊泡运输和细胞骨架组织。在这里，我们研究了Pacsin 2在肾脏损伤后的发育和修复中的作用。在出生后发育的肾脏中，Pacsin 2在输尿管芽和间质来源的结构中都有表达，包括近端和远端的小管、Bowman囊和肾小球束。在成人肾脏中，与发育中的肾脏相比，其在近端小管中的表达减少，而在肾小球小球中的表达增加。有趣的是，在缺血再灌注损伤后的修复阶段，Pacsin 2的表达显著上调，尤其是在经历了大量损伤的近端小管的顶端刷状边缘。Pacsin 2定位于肾上皮细胞的初级纤毛。ShRNA敲除Pacsin 2对细胞周期和细胞极性没有影响，但增加了原生纤毛的长度，并导致三维细胞培养中明显的管状生成缺陷。因此，我们认为Pacsin 2以一种肾单位特异性的方式促进肾脏的发育和修复。《国际肾脏》(2013年)83,426-437；doi：10.1038/ki.2012.379；2012年12月12日在线发布
The protein kinase C and casein kinase 2 substrate in neurons (Pacsin) is a subfamily of membrane-binding proteins that participates in vesicle trafficking and cytoskeleton organization. Here, we studied Pacsin 2 in kidney development and repair following injury. In the postnatal developing kidneys, Pacsin 2 was found to be expressed in both ureteric bud- and mesenchyme-derived structures including proximal and distal tubules, Bowman's capsule, and the glomerular tuft. In the adult kidney, its expression was decreased in proximal tubules but increased in glomerular tuft when compared to that in the developing kidneys. Interestingly, Pacsin 2 expression was significantly upregulated during the repair phase after ischemia-reperfusion injury, especially on the apical brush border of proximal tubules that experienced massive damage. Pacsin 2 localized to the primary cilia of renal epithelial cells. Knockdown of Pacsin 2 by shRNA did not affect the cell cycle or cell polarity; however, it increased the length of primary cilia, and resulted in significant tubulogenic defects in three-dimensional cell culture. Thus, we propose that Pacsin 2 contributes to kidney development and repair in a nephron-specific manner. Kidney International (2013) 83, 426-437; doi:10.1038/ki.2012.379; published online 12 December 2012