Mechanotransduction by TRP Channels: General Concepts and Specific Role in the Vasculature
Mechanotransduction by TRP Channels: General Concepts and Specific Role in the Vasculature
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DOI：
10.1007/s12013-009-9067-2
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发表时间：
2009
影响因子：
2.6
通讯作者：
Junyan Yin;W. Kuebler
中科院分区：
文献类型：
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作者：
Junyan Yin;W. Kuebler
瞬时受体电位（TRP）离子通道超家族参与多种外部或内部刺激的感知和传递，包括但不限于机械应力。基于同源性分析，遗传和分子研究最近已经在包括血管的不同组织中鉴定了TRP通道。在无脊椎动物中，许多TRP通道（包括在秀丽隐杆线虫中鉴定的5个TRPV通道和在果蝇中鉴定的2个TRPV通道）作为音量调节、听觉和触觉敏感性的分子基础参与机械感觉行为。同样，在哺乳动物中，许多TRP家族成员如TRPC 1、TRPC 3、TRPC 6、TRPM 4、TRPM 7、TRPN 1、TRPA 1、TRPY 1、TRPP 1、TRPP 2，特别是TRPV 1、TPRV 2以及TRPV 4已被报道参与机械转导。本文综述了最近的研究结果，有时有争议的作用和调节TRP通道在机械转导。具体而言，我们强调TRPV通道在血管调节中的相关性，并关注肺血管系统中的TRPV4，该系统不断暴露于周向和纵向应变的独特组合。根据我们在完整的肺微血管中观察到的机械应力诱导的内皮细胞中的Ca 2+信号传导与TRPV4活性密切相关，我们推测TRPV4在肺血管机械转导中起关键作用。在这个迅速扩大的领域的进展可能会允许识别新的分子靶点，并在一些与机械应力有关的顽固性疾病的新的治疗方法的发展。
Transient receptor potential (TRP) ion channel superfamily is involved in sensing and transmission of a broad variety of external or internal stimuli, including but not limited to mechanical stress. Based on homology analysis, genetic and molecular studies have recently identified TRP channels in different tissues, comprising blood vessels. In invertebrates, many TRP channels including five TRPV channels identified inCaenorhabditis elegansand two inDrosophilahave been implicated in mechanosensory behaviors as molecular basis of volume regulation, hearing and touch sensitivity. Consistently, in mammals many TRP family members such as TRPC1, TRPC3, TRPC6, TRPM4, TRPM7, TRPN1, TRPA1, TRPY1, TRPP1, TRPP2, and notably, TRPV1, TPRV2 as well as TRPV4 have been reported to be involved in mechanotransduction. This review summarizes recent and at times controversial findings on the role and regulation of TRP channels in mechanotransduction. Specifically, we highlight the relevance of TRPV channels in vascular regulation and focus on TRPV4 in the vascular system of the lung, which is constantly exposed to a unique combination of circumferential and longitudinal strains. In light of our observation in intact pulmonary microvessels that mechanical stress induced Ca2+signaling in endothelial cells is closely related to TRPV4 activity, we postulate that TRPV4 plays a critical role in lung vascular mechanotransduction. The progress in this rapidly expanding field may allow for the identification of new molecular targets and the development of new therapeutic approaches in a number of intractable diseases related to mechanical stress.