Novel insights into TRPV4 function in the kidney.
Novel insights into TRPV4 function in the kidney.
复制标题
对肾脏中TRPV4功能的新颖见解。
DOI：
10.1007/s00424-012-1190-z
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发表时间：
2013-02
影响因子：
4.5
通讯作者：
Mamenko, Mykola
中科院分区：
文献类型：
--
作者：
Pochynyuk, Oleh;Zaika, Oleg;O'Neil, Roger G.;Mamenko, Mykola
关键词：
肾脏是一个复杂的、高度组织化的成对器官，每个器官有近一百万个肾单位。他们每天严格处理约180升血浆，以保持全身的稳态。为了有效地执行这种巨大的工作，肾脏依赖于能够感测沿着肾小管沿着的原尿嘧啶的组成和流速的动态变化的机制。可以设想，Ca2+渗透性瞬时受体电位通道（TRP），特别是机械敏感性TRPV 4，可以用于以升高的细胞内Ca2+浓度（[Ca2+]i）的形式解释这些外部机械线索。这反过来又启动了多种细胞反应和适应机制。目前的审查总结了最新的知识TRPV4在肾组织中的表达的网站，以及讨论的功能作用的通道在细胞反应低渗和肾小管流量。我们还将提供有关TRPV4如何适应纤毛中的经典多囊蛋白机械感觉复合物的见解，并将推测以前未被充分认识的药理学TRPV4靶向治疗多囊肾病的临床意义。
Kidneys are complex highly organized paired organs of nearly 1 million nephrons each. They rigorously process about 180 liters of plasma daily to keep whole body homeostasis. To effectively perform such a titanic work, kidneys rely on mechanisms able to sense dynamic changes in composition and flow rates of protourine along the renal tubule. It is envisioned that Ca2+ permeable transient receptor potential channels (TRPs), and specifically mechanosensitive TRPV4, can serve to interpret these external mechanical cues in the form of elevated intracellular Ca2+ concentration ([Ca2+]i). This, in turn, initiates multiple cellular responses and adaptation mechanisms. The current review summarizes up-to-date knowledge about the sites of TRPV4 expression in renal tissue as well as discusses the functional role of the channel in cellular responses to hypotonicity and tubular flow. We will also provide insights as to how TRPV4 fits into classical polycystin mechanosensory complex in cilia and will speculate about previously underappreciated clinical implication of pharmacological TRPV4 targeting in treatment of polycystic kidney disease.
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