Yes, no, maybe so: ENaC proteins as mediators of renal myogenic constriction.
Yes, no, maybe so: ENaC proteins as mediators of renal myogenic constriction.
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是的，不，也许是这样：ENaC 蛋白作为肾肌源性收缩的介质。
DOI：
10.1161/hypertensionaha.109.139014
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Drummond,HeatherA
中科院分区：
文献类型：
--
作者：
Drummond,HeatherA
肌源性反应是一种固有的血管反应，其特征在于对灌注压升高的血管收缩和对灌注压降低的血管舒张。最近的研究表明，这种反应可能在保护肾微循环免受压力依赖性损伤方面发挥重要作用，特别是伴随肾脏疾病。[1]虽然肌源性反应在100多年前就被首次描述，但在血管平滑肌细胞（VSMCs）中，压力转导成细胞事件（即血管收缩）的分子机制仍然难以捉摸。已经鉴定了与机械敏感性反应相关的几种潜在分子，包括整联蛋白、瞬时受体电位（TRP）通道和上皮Na+通道（ENaC）家族的成员。2 ENaC家族成员最近受到关注，因为有证据支持和反对ENaC蛋白在肾循环中的肌源性收缩中的作用。Guan等人的当前研究有助于解决ENaC在传入小动脉肌源性收缩中的争议性作用。3ENaC和密切相关的酸敏感离子通道（ASIC）蛋白被认为是VSMC中潜在的机械转导子，因为它们与一组称为退化蛋白的蛋白质有很强的进化联系。简并蛋白是一组线虫秀丽隐杆线虫蛋白质，其在大的多聚体机械感觉复合物中包含离子通道孔。4遗传证据表明，成孔变性蛋白与细胞骨架和细胞外基质相连，并有助于力传递。4细胞外基质、连接蛋白和细胞骨架蛋白是适当的机械传感器通道激活所必需的。[4]哺乳动物中的类似机械换能器模型也已提出（图1A）。尽管许多科学家认为ENaC蛋白仅限于上皮细胞，但ENaC表达已在许多其他细胞类型（包括VSMC）中反复鉴定。5一些研究支持ENaC蛋白作为肾叶间动脉和大脑中动脉中肌源性反应的介质的作用。ENaC蛋白在来自几个循环系统的VSMC中表达。此外，ENaC抑制（阿米洛利或其亲脂性类似物苯扎明）
The myogenic response is an intrinsic vascular response characterized by vasoconstriction in response to increases and vasodilation to decreases in perfusion pressure. Recent studies suggest this response may play a significant role in the protection of the renal microcirculation from pressure dependent injury, especially with concomitant renal disease. 1 Although the myogenic response was first described more than 100 years ago, the molecular mechanisms underlying the transduction of pressure into a cellular event (ie, vasoconstriction) in vascular smooth muscle cells (VSMCs) has remained elusive. Several potential molecules with a connection to mechanosensitive responses have been identified including integrins, transient receptor potential (TRP) channels, and members of the Epithelial Na+ Channel (ENaC) family. 2 Members of the ENaC family have received recent attention because of evidence for and against a role for ENaC proteins in myogenic constriction in the renal circulation. The current study by Guan et al helps to address the controversial role of ENaC in afferent arteriolar myogenic constriction. 3ENaC and closely related Acid Sensing Ion Channel (ASIC) proteins are considered potential mechanotransducers in VSMCs because of their strong evolutionary connection to a group of proteins termed degenerins. The degenerins are a group of nematode Caenorhabditis elegans proteins that comprise the ion channel pore in a large multimeric mechanosensory complex. 4 Genetic evidence suggests the pore forming degenerins are tethered to the cytoskeleton and extracellular matrix and aid in force transduction. 4 The extracellular matrix, linking proteins, and cytoskeletal proteins are required for proper mechanosensor channel activation. 4 An analogous mechanotransducer model in mammals has also been proposed (Figure 1A). 5 Although many scientists consider ENaC proteins to be restricted to epithelial cells, ENaC expression has been repeatedly identified in many other cells types, including VSMCs. 5 Several studies support a role for ENaC proteins as mediators of myogenic responsiveness in renal interlobar and middle cerebral arteries. ENaC proteins are expressed in VSMCs from several circulatory systems. Furthermore, ENaC inhibition (amiloride or its lipophilic analog benzamil)