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瞬时受体电位通道与肺血管内皮通透性的调节。

Transient receptor potential channels and regulation of lung endothelial permeability.

机构信息

Departments of Physiology and Medicine, Center for Lung Biology, University of South Alabama, Mobile, Alabama, USA.

出版信息

Pulm Circ. 2013 Dec;3(4):802-15. doi: 10.1086/674765.

DOI:10.1086/674765
PMID:25006396
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4070837/
Abstract

This review highlights our current knowledge regarding expression of transient receptor potential (TRP) cation channels in lung endothelium and evidence for their involvement in regulation of lung endothelial permeability. Six mammalian TRP families have been identified and organized on the basis of sequence homology: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPA (ankyrin). To date, only TRPC1/4, TRPC6, TRPV4, and TRPM2 have been extensively studied in lung endothelium. Calcium influx through each of these channels has been documented to increase lung endothelial permeability, although their channel-gating mechanisms, downstream signaling mechanisms, and impact on endothelial structure and barrier integrity differ. While other members of the TRPC, TRPV, and TRPM families may be expressed in lung endothelium, we have little or no evidence linking these to regulation of lung endothelial permeability. Further, neither the expression nor functional role(s) of any TRPML, TRPP, and TRPA family members has been studied in lung endothelium. In addition to this assessment organized by TRP channel family, we also discuss TRP channels and lung endothelial permeability from the perspective of lung endothelial heterogeneity, using outcomes of studies focused on TRPC1/4 and TRPV4 channels. The diversity within the TRP channel family and the relative paucity of information regarding roles of a number of these channels in lung endothelium make this field ripe for continued investigation.

摘要

这篇综述强调了我们目前对于肺内皮细胞中瞬时受体电位 (TRP) 阳离子通道表达的了解,并提供了这些通道参与肺内皮通透性调节的证据。已经确定了六个哺乳动物 TRP 家族,并根据序列同源性进行了组织:TRPC(经典)、TRPV(香草酸)、TRPM(melastatin)、TRPML(粘脂)、TRPP(多囊蛋白)和 TRPA(锚蛋白)。迄今为止,在肺内皮细胞中已经广泛研究了 TRPC1/4、TRPC6、TRPV4 和 TRPM2。已经证明,这些通道中的每一个通道的钙内流都会增加肺内皮通透性,尽管它们的通道门控机制、下游信号机制以及对内皮结构和屏障完整性的影响不同。虽然 TRPC、TRPV 和 TRPM 家族的其他成员可能在肺内皮细胞中表达,但我们几乎没有或没有证据将这些成员与肺内皮通透性的调节联系起来。此外,TRPML、TRPP 和 TRPA 家族成员的表达或功能作用在肺内皮细胞中均未得到研究。除了按 TRP 通道家族进行评估外,我们还从肺内皮细胞异质性的角度讨论了 TRP 通道和肺内皮通透性,使用了专注于 TRPC1/4 和 TRPV4 通道的研究结果。TRP 通道家族内的多样性以及这些通道中许多在肺内皮细胞中的作用的信息相对较少,使得这一领域非常适合进一步研究。

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本文引用的文献

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Endothelial calcium dynamics, connexin channels and blood-brain barrier function.内皮细胞钙离子动力学、连接蛋白通道与血脑屏障功能。
Prog Neurobiol. 2013 Sep;108:1-20. doi: 10.1016/j.pneurobio.2013.06.001. Epub 2013 Jul 10.
2
An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure.一种口服有效的 TRPV4 通道阻滞剂可预防和治疗心力衰竭引起的肺水肿。
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Recruitment of dynamic endothelial Ca2+ signals by the TRPA1 channel activator AITC in rat cerebral arteries.辣椒素激活瞬时受体电位通道蛋白 A1 招募大鼠脑动脉内皮细胞中的动态钙离子信号。
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Orai1 determines calcium selectivity of an endogenous TRPC heterotetramer channel.Orai1 决定内源性 TRPC 杂四聚体通道的钙离子选择性。
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The ion channel transient receptor potential melastatin-2 does not play a role in inflammatory mouse models of chronic obstructive pulmonary diseases.瞬时受体电位通道亚家族 M 成员 2 离子通道在慢性阻塞性肺疾病的炎症小鼠模型中不起作用。
Respir Res. 2012 Apr 4;13(1):30. doi: 10.1186/1465-9921-13-30.
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Activation of TRPC6 channels is essential for lung ischaemia-reperfusion induced oedema in mice.TRPC6 通道的激活对于小鼠肺缺血再灌注引起的水肿是必不可少的。
Nat Commun. 2012 Jan 31;3:649. doi: 10.1038/ncomms1660.
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Lung endothelial Ca2+ and permeability response to platelet-activating factor is mediated by acid sphingomyelinase and transient receptor potential classical 6.肺内皮细胞对血小板激活因子的 Ca2+和通透性反应是由酸性鞘磷脂酶和瞬时受体电位经典型 6 介导的。
Am J Respir Crit Care Med. 2012 Jan 15;185(2):160-70. doi: 10.1164/rccm.201104-0717OC.
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Critical role of TRPP2 and TRPC1 channels in stretch-induced injury of blood-brain barrier endothelial cells.TRPP2 和 TRPC1 通道在拉伸诱导的血脑屏障内皮细胞损伤中的关键作用。
Brain Res. 2012 Feb 3;1436:1-12. doi: 10.1016/j.brainres.2011.11.044. Epub 2011 Dec 1.
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The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation.氧化还原敏感阳离子通道 TRPM2 调节吞噬细胞 ROS 产生和炎症反应。
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