Primary cilia of inv/inv mouse renal epithelial cells sense physiological fluid flow:: Bending of primary cilia and Ca2+ influx
Primary cilia of inv/inv mouse renal epithelial cells sense physiological fluid flow:: Bending of primary cilia and Ca2+ influx
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DOI：
10.1247/csf.30.93
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发表时间：
2005-12-01
影响因子：
1.5
通讯作者：
Yokoyama, T
中科院分区：
文献类型：
--
作者：
Shiba, D;Takamatsu, T;Yokoyama, T
初级纤毛被认为是检测肾小管液体流动的机械传感器。原生纤毛结构的异常和/或流体流动引起的细胞内钙离子浓度升高被认为是条件kif3a基因敲除、Tg737和PKD1/PKD2突变小鼠形成肾囊的原因。突变inv/inv小鼠发生了多个肾囊肿，如kif3a、Tg737和PKD1/PKD2突变。INV蛋白定位于肾初级纤毛，但INV/INV纤毛对液体应激的反应尚未被研究。在本研究中，我们用视频显微镜观察了原生纤毛对生理性血流的机械反应，以及正常和inv/inv小鼠肾上皮细胞对流应激反应中细胞内钙离子的增加。原代培养的正常和inv/inv突变小鼠肾细胞纤毛细胞百分率和纤毛长度无显著差异。即使在现在的胁迫下，inv蛋白的定位仍然局限于初生纤毛的底部。与正常细胞相比，inv/inv突变细胞具有与正常细胞相似的原生纤毛弯曲机制。此外，在正常和inv/inv突变细胞中，细胞内钙离子对生理性液体流动的反应没有发现差异。我们目前的研究表明，inv蛋白的功能不同于Polaris(Tg737基因产物)、多囊蛋白(PKD1和PKD2基因产物)。
Primary cilia are hypothesized to act as a mechanical sensor to detect renal tubular fluid flow. Anomalous structure of primary cilia and/or impairment of increases in intracellular Ca2+ concentration in response to fluid flow are thought to result in renal cyst formation in conditional kif3a knockout, Tg737 and pkd1/pkd2 mutant mice.The mutant inv/inv mouse develops multiple renal cysts like kif3a, Tg737 and pkd1/pkd2 mutants. Inv proteins have been shown to be localized in the renal primary cilia, but response of inv/inv cilia to fluid stress has not been examined. In the present study, we examined the mechanical response of primary cilia to physiological nuid flow using a video microscope, as well as intracellular Ca2+ increases in renal epithelial cells from normal and inv/inv mice in response to flow stress. Percentages of ciliated cells and the length of primary cilia were not significantly different between primary renal cell cultures from normal and inv/inv mutant mice. Localization of inv protein was restricted to the base of primary cilia even under now stress. Inv/inv mutant cells had similar bending mechanics of primary cilia in response to physiological nuid flow compared to normal cells. Furthermore, no difference was found in intracellular Ca2+ increases in response to physiological fluid flow between normal and inv/inv mutant cells. Our present study suggests that the function of the inv protein is distinct from polaris (the Tg737 gene product), polycystins (pkd1 and pkd2 gene products).