Aberrant planar cell polarity induced by urinary tract obstruction
Aberrant planar cell polarity induced by urinary tract obstruction
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DOI：
10.1152/ajprenal.00318.2009
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发表时间：
2009-12-01
影响因子：
4.2
通讯作者：
Lin, Fangming
中科院分区：
文献类型：
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作者：
Li, Ling;Zepeda-Orozco, Diana;Lin, Fangming
李L，Zepeda-Orozco D，Patel V，Truong P，Karner CM，卡罗尔TJ，Lin F.尿路梗阻引起的平面细胞极性异常。美国肾脏生理学杂志297：F1526-F1533，2009年。首次发表于2009年9月30日; doi：10.1152/ajprenal.00318.2009.-上皮细胞初级纤毛的流量感应参与多囊肾囊肿形成我们研究是否有类似的机制适用于小鼠输尿管梗阻引起的囊肿样肾小管扩张的发病机制。当尿流中断时，在阻塞的小管中发生稳健的增殖，以及当尿流在阻塞解除后重新建立时，在修复的小管中发生稳健的增殖，这表明了不依赖于尿流的增殖机制。在尿路上皮中，仅在梗阻上方检测到增生，尽管梗阻上方和下方的尿流均停止。我们的研究结果支持梗阻性尿路病的机械应变，而不是流量介导的增殖。为了了解细胞增殖导致囊样肾小管扩张中肾小管直径增加的机制，我们研究了平面细胞极性（PCP），这是定向细胞分裂和维持肾小管直径所必需的。在扩张的小管中，细胞分裂的方向是随机的，非典型PKC（aPKC）被错误定位，并且核心PCP蛋白Frizzled 3（Fz 3）的表达模式被改变。此外，Fz 3表达水平增加。这些结果表明，异常PCP可能有助于梗阻性尿路病的囊肿样肾小管扩张。有趣的是，当梗阻缓解时，细胞分裂方向、aPKC定位和Fz 3表达恢复正常，这表明正常PCP信号传导在肾小管修复中的作用。
Li L, Zepeda-Orozco D, Patel V, Truong P, Karner CM, Carroll TJ, Lin F. Aberrant planar cell polarity induced by urinary tract obstruction. Am J Physiol Renal Physiol 297: F1526-F1533, 2009. First published September 30, 2009; doi:10.1152/ajprenal.00318.2009.-Flow sensing by primary cilia of the epithelial cells is involved in cystogenesis in polycystic kidney disease. We investigate whether a similar mechanism applies to the pathogenesis of cyst-like tubular dilatation induced by ureteral obstruction in mice. Robust proliferation occurs in the obstructed tubules when urine flow is interrupted as well as in the repairing tubules when urine flow is reestablished after relief of the obstruction, suggesting a urine flow-independent mechanism of proliferation. In the urothelium, proliferation is only detected above the obstruction, although urine flow ceased both above and below the obstruction. Our results support mechanical strain-rather than flow-mediated proliferation in obstructive uropathy. To understand the mechanism of cell proliferation leading to increased tubular diameter in cyst-like tubular dilatation, we examine planar cell polarity (PCP), which is necessary for oriented cell division and maintenance of tubular diameter. In dilated tubules, the orientation of cell division is randomized, atypical PKC (aPKC) is mislocalized, and the pattern of the expression of a core PCP protein, Frizzled3 (Fz3), is altered. In addition, the level of Fz3 expression is increased. These results indicate that aberrant PCP may contribute to cyst-like tubular dilatation in obstructive uropathy. Interestingly, the orientation of cell division, localization of aPKC, and Fz3 expression return to normal when obstruction is relieved, which suggest a role of normal PCP signaling in tubular repair.