Epidermal growth factor-mediated proliferation and sodium transport in normal and PKD epithelial cells.
Epidermal growth factor-mediated proliferation and sodium transport in normal and PKD epithelial cells.
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DOI：
10.1016/j.bbadis.2010.10.004
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发表时间：
2011-10
影响因子：
6.2
通讯作者：
Staruschenko, Alexander
中科院分区：
文献类型：
--
作者：
Zheleznova, Nadezhda N.;Wilson, Patricia D.;Staruschenko, Alexander
表皮生长因子（EGF）家族成员与ErbB （EGFR）家族受体结合，在包括细胞增殖和分化在内的各种基本细胞过程的调节中发挥重要作用。正常的啮齿动物肾脏已被证明表达至少三个ErbB受体家族成员，并且是EGF配体合成的主要部位。多囊肾病（Polycystic kidney disease， PKD）是一组由单基因突变引起的疾病，其特征是双肾内形成多个囊肿而导致肾脏增大。小管细胞增生，引起节段扩张，与几种蛋白质的异常沉积有关。在PKD发病机制的细胞生物学研究中，首先描述的异常之一是囊肿内膜上皮细胞中EGFR的异常错定位。肾集管（CD）主要是一种吸收性上皮，其中电致Na+进入是由上皮Na+通道（ENaC）介导的。enact介导的钠吸收是CD中一个重要的离子转运途径，可能参与PKD的发生。EGF在enact介导的钠吸收调控中的作用已被提出。然而，一些研究报告了相互矛盾的结果，表明EGF及其相关因素对ENaC活性和钠转运的相反作用。本文讨论了egf家族蛋白如何调节正常上皮细胞和PKD上皮细胞的增殖和钠转运的最新进展。
Members of the epidermal growth factor (EGF)-family bind to ErbB (EGFR)-family receptors which play an important role in the regulation of various fundamental cell processes including cell proliferation and differentiation. The normal rodent kidney has been shown to express at least three members of the ErbB receptor family and is a major site of EGF ligand synthesis. Polycystic kidney disease (PKD) is a group of diseases caused by mutations in single genes and is characterized by enlarged kidneys due to the formation of multiple cysts in both kidneys. Tubule cells proliferate, causing segmental dilation, in association with the abnormal deposition of several proteins. One of the first abnormalities described in cell biological studies of PKD pathogenesis was the abnormal mislocalization of the EGFR in cyst lining epithelial cells. The kidney collecting duct (CD) is predominantly an absorptive epithelium where electrogenic Na+ entry is mediated by the epithelial Na+ channel (ENaC). ENaC-mediated sodium absorption represents an important ion transport pathway in the CD that might be involved in the development of PKD. A role for EGF in the regulation of ENaC-mediated sodium absorption has been proposed. However, several investigations have reported contradictory results indicating opposite effects of EGF and its related factors on ENaC activity and sodium transport. Recent advances in understanding how proteins in the EGF-family regulate the proliferation and sodium transport in normal and PKD epithelial cells are discussed here.
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