Signal transduction in podocytes--spotlight on receptor tyrosine kinases.
Signal transduction in podocytes--spotlight on receptor tyrosine kinases.
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DOI：
10.1038/nrneph.2013.274
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发表时间：
2014-02
影响因子：
41.5
通讯作者：
Faul, Christian
中科院分区：
文献类型：
--
作者：
Reiser, Jochen;Sever, Sanja;Faul, Christian
哺乳动物肾脏滤过屏障是一种复杂的多细胞、多组分结构，通过调节电解质、酸碱平衡和血压（通过维持盐和水平衡）来维持体内平衡。为了完成这些多重功能，足细胞-过滤装置的重要组成部分-必须处理一系列细胞间信号。将这些信号与不同的细胞响应相结合，能够对各种条件进行协调响应。虽然成熟的足细胞是终末分化的，不能增殖，但它们能够对生长因子作出反应。足细胞对生长因子的初始反应可能是有益的和保护性的，并且可能包括肥大细胞生长的诱导。然而，延长和/或不受控制的生长因子信号可能是适应不良的，并可能导致诱导凋亡和足细胞损失。生长因子通过其靶细胞上的受体酪氨酸激酶（RTK）的激活发出信号，并且在人类基因组中编码的58个RTK家族成员中约有四分之一已在足细胞中鉴定。存在许多RTK的药理学抑制剂，目前用于实验和临床癌症治疗。在足细胞中病理性RTK介导的信号转导通路的鉴定可以为肾小球疾病的新疗法的开发提供起点。
The mammalian kidney filtration barrier is a complex multicellular, multicomponent structure that maintains homeostasis by regulating electrolytes, acid–base balance, and blood pressure (via maintenance of salt and water balance). To perform these multiple functions, podocytes—an important component of the filtration apparatus—must process a series of intercellular signals. Integrating these signals with diverse cellular responses enables a coordinated response to various conditions. Although mature podocytes are terminally differentiated and cannot proliferate, they are able to respond to growth factors. It is possible that the initial response of podocytes to growth factors is beneficial and protective, and might include the induction of hypertrophic cell growth. However, extended and/or uncontrolled growth factor signalling might be maladaptive and could result in the induction of apoptosis and podocyte loss. Growth factors signal via the activation of receptor tyrosine kinases (RTKs) on their target cells and around a quarter of the 58 RTK family members that are encoded in the human genome have been identified in podocytes. Pharmacological inhibitors of many RTKs exist and are currently used in experimental and clinical cancer therapy. The identification of pathological RTK-mediated signal transduction pathways in podocytes could provide a starting point for the development of novel therapies for glomerular disorders.
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影响因子：
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作者：
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DOI：
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