Neutrophil gelatinase-associated lipocalin suppresses cyst growth by Pkd1 null cells in vitro and in vivo.
Neutrophil gelatinase-associated lipocalin suppresses cyst growth by Pkd1 null cells in vitro and in vivo.
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DOI：
10.1038/ki.2008.395
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发表时间：
2008-11
影响因子：
19.6
通讯作者：
Cantley, Lloyd G.
中科院分区：
文献类型：
--
作者：
Wei, Feng;Karihaloo, Anil;Yu, Zhiheng;Marlier, Arnaud;Seth, Pankaj;Shibazaki, Sekiya;Wang, Tong;Sukhatme, Vikas P.;Somlo, Stefan;Cantley, Lloyd G.
常染色体显性遗传性多囊肾病患者的囊肿生长被认为是由于肾小管细胞增殖增加。一个模型来解释这种改变的增殖表明，多囊蛋白PC1和PC2定位于顶端纤毛，并作为一个组成部分的流量传感途径，从而调节增殖反应。我们在缺乏PC1的近端小管衍生细胞系中测量增殖和凋亡。与对照杂合细胞系相比，这些细胞显示出增殖速率增加，凋亡速率降低，并且在体外小管形成测定中自发形成囊肿而不是小管。此外，中性粒细胞明胶酶相关脂质运载蛋白（NGAL），一个小的分泌蛋白，结合不同的配体，细胞缺乏PC1抑制增殖和增加细胞凋亡，导致较慢的囊肿生长在体外。在Pkd1突变小鼠中，通过腺病毒递送系统以低水平持续过度表达NGAL抑制囊肿扩大而不改善肾功能。我们的研究表明，缺乏PC1的肾上皮细胞在体外具有过度增殖形成囊肿的内在倾向，而不依赖于流动刺激。NGAL减弱囊肿生长的潜在益处仍有待确定。
Cyst growth in patients with autosomal dominant polycystic kidney disease is thought to be due to increased tubular cell proliferation. One model to explain this altered proliferation suggests that the polycystin proteins PC1 and PC2 localize to apical cilia and serve as an integral part of the flow-sensing pathway thus modulating the proliferative response. We measured proliferation and apoptosis in proximal tubule derived cell lines lacking PC1. These cells showed increased rates of proliferation, a decreased rate of apoptosis, compared to control heterozygous cell lines, and spontaneously formed cysts rather than tubules in an in vitro tubulogenesis assay. Addition of neutrophil gelatinase associated lipocalin (NGAL), a small secreted protein that binds diverse ligands, to the cells lacking PC1 inhibited proliferation and increased apoptosis leading to slower cyst growth in vitro. Sustained over-expression at low level of NGAL by an adenoviral delivery system suppressed cyst enlargement without improving renal function in the Pkd1 mutant mice. Our studies show that renal epithelial cells lacking PC1 have an inherent tendency to hyper-proliferate forming cysts in vitro independent of a flow stimulus. The potential benefit of attenuating cyst growth with NGAL remains to be determined.
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影响因子：
21.3
作者：
Li, XG;Luo, Y;Zhou, J
通讯作者：
Zhou, J
影响因子：
82.9
作者：
Fink, L;Seeger, W;Bohle, RM
通讯作者：
Bohle, RM
影响因子：
2.9
作者：
Goetz, DH;Willie, ST;Strong, RK
通讯作者：
Strong, RK
DOI：
10.1152/ajprenal.00015.2004
发表时间：
2004-10-01
影响因子：
4.2
作者：
Chen, D;Roberts, R;Zent, R
通讯作者：
Zent, R
影响因子：
3.5
作者：
Hvidberg, V;Jacobsen, C;Borregaard, N
通讯作者：
Borregaard, N