EGF and Its Related Growth Factors Mediate Sodium Transport in mpkCCDc14 Cells via ErbB2 (neu/HER-2) Receptor
EGF and Its Related Growth Factors Mediate Sodium Transport in mpkCCDc14 Cells via ErbB2 (neu/HER-2) Receptor
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DOI：
10.1002/jcp.22033
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发表时间：
2010-04-01
影响因子：
5.6
通讯作者：
Staruschenko, Alexander
中科院分区：
文献类型：
--
作者：
Levchenko, Vladislav;Zheleznova, Nadezhda N.;Staruschenko, Alexander
通过上皮钠通道（ENaC）的阿米洛利敏感性钠内流是Na+吸收的限速步骤。表皮生长因子（EGF）参与Na+转运和ENaC活性的调节。然而，EGF如何调节ENaC和Na+吸收仍然存在争议。本研究的目的是描述EGF调节培养的小鼠肾集合管主要mpkCCD（C14）细胞，一个高度分化的细胞系，保留了许多特征的皮质集合管（CCD）的Na+运输。EGF剂量依赖性调节基础跨上皮Na+转运分为两个阶段：急性期（< 4小时）和慢性期（> 8小时）。TGF-α、HB-EGF和双调蛋白（也属于EGF相关肽生长因子家族）也观察到类似的作用。通过PD 98059或U 0126抑制MEK 1/2增加了EGF对Na+重吸收的急性效应并破坏了EGF对Na+重吸收的慢性效应。用LY 294002抑制PI 3-激酶可消除EGF的急性效应。如通过蛋白质印迹法所评估的，ErbB 2是在mpkCCD（c14）细胞中检测到的ErbB家族的最主要成员。免疫组织化学分析显示ErbB 2在Sprague道利大鼠肾脏CCD中的定位。当细胞用tyrphostin AG-825和ErbB 2抑制剂II（ErbB 2受体的化学上不同的选择性抑制剂）处理时，EGF的急性和长期作用均被消除。因此，我们得出结论，EGF及其相关的生长因子是重要的维持跨上皮Na+运输和EGF双相调节钠转运mpkCCD（C14）细胞通过ErbB 2受体。J.细胞。223：252-259，2010。(c)2010 Wiley-Liss，Inc.
Amiloride-sensitive sodium entry, via the epithelial sodium channel (ENaC), is the rate-limiting step for Na+ absorption. Epidermal growth factor (EGF) is involved in the regulation of Na+ transport and ENaC activity. However it is still controversial exactly how EGF regulates ENaC and Na+ absorption. The aim of the present study was to characterize the EGF regulation of Na+ transport in cultured mouse renal collecting duct principal mpkCCD(c14) cells, a highly differentiated cell line which retains many characteristics of the cortical collecting duct (CCD). EGF dose dependently regulates basal transepithelial Na+ transport in two phases: an acute phase (< 4 h) and a chronic phase (> 8 h). Similar effects were observed with TGF-alpha, HB-EGF, and amphiregulin which also belong to the EGF-related peptide growth factor family. Inhibition of MEK1/2 by PD98059 or U0126 increased acute effects and disrupted chronic effects of EGF on Na+ reabsorption. Inhibition of PI3-kinase with LY294002 abolished acute effect of EGF. As assessed by Western blotting, ErbB2 is the most predominant member of the ErbB family detected in mpkCCD(c14) cells. Immunohistochemistry analysis revealed localization of ErbB2 in the CCD in Sprague Dawley rat kidneys. Both acute and long-term effects of EGF were abolished when cells were treated with tyrphostin AG-825 and ErbB2 inhibitor II, chemically dissimilar selective inhibitors of the ErbB2 receptor. Thus, we conclude that EGF and its related growth factors are important for maintaining transepithelial Na+ transport and that EGF biphasically modulates sodium transport in mpkCCD(c14) cells via the ErbB2 receptor. J. Cell. Physiol. 223: 252-259, 2010. (c) 2010 Wiley-Liss, Inc.