Regulating cross-talk between vascular smooth muscle cells.
Regulating cross-talk between vascular smooth muscle cells.
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调节血管平滑肌细胞之间的串扰。
DOI：
10.1161/01.atv.0000093820.81258.5f
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Tulenko,ThomasN
中科院分区：
文献类型：
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作者：
Tulenko,ThomasN
间隙连接是邻近细胞之间形成小孔的蛋白质连接，介导离子和小分子的流动（1 200 Da）。因此，它们在细胞之间提供了一定程度的直接细胞质连续性，与旁分泌途径一起有助于细胞间的信息流动。这些通道通常被认为是长寿命的、非特异性的通道，允许离子电流和小信号分子（如cAMP、cGMP等）在细胞间传播。然而，近年来，新的证据极大地提高了我们对它们的多样性、调控和对正常组织功能的贡献的认识，更重要的是，提高了我们对各种疾病发病机制的理解。例如，在肿瘤学中，各种癌症中恶性细胞的生长和扩散似乎依赖于在正常细胞和恶性细胞之间建立间隙连接连接。1,2在心血管医学中，间隙连接的改变与心律失常的发生、高血压的动脉壁重塑、4-6以及动脉粥样硬化有关。7-9事实上，这个名单还在继续，包括眼科、神经系统、胃肠道和内分泌系统的病理。考虑到它们参与组织生理学和病理生理学，我们有必要进一步揭示间隙连接蛋白表达和功能的调控机制。在这一期的《动脉硬化、血栓形成和血管生物学》中，Cowan和他在多伦多和波士顿的同事们描述了一系列优雅的实验，证明血管平滑肌细胞中的主要间隙连接蛋白Cx43在缺氧和拉伸的作用下转录上调，而这令人惊讶地显示是由活性氧（ROS）的形成介导的。
Gap junctions are small pore-forming protein connec-tions between neighboring cells that mediate the flow of ions and small molecules (1 200 Da). As such, they provide a degree of direct cytoplasmic continuity between cells that contributes, along with paracrine pathways, to the intercellular flow of information. These channels are often thought to be long-lived, nonspecific conduits allowing the cell-to-cell spread of ionic currents and small signaling molecules such as cAMP, cGMP, etc. However, in recent years, new evidence has dramatically improved our appreciation of their diversity, regulation, and contribution to normal tissue function and, importantly, has advanced our understanding of the pathogenesis of various diseases. For example, in oncology, the growth and spread of malignant cells in a variety of cancers appears to be dependent on establishing gap junction connections between normal and malignant cells. 1, 2 In cardiovascular medicine, gap junction alterations have been implicated in the genesis of cardiac arrhythmias, 3 remodeling of the arterial wall in hypertension, 4–6 and perhaps atherosclerosis. 7–9 Indeed, the list goes on, including pathologies in the ophthalmic, neurologic, gastrointestinal, and endocrine systems. Considering their involvement in tissue physiology and pathophysiology, it is essential that we move forward in unraveling the regulatory mechanisms underlying gap junction protein expression and function. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Cowan and his colleagues10 in Toronto and Boston describe an elegant series of experiments demonstrating that the principle gap junction protein in vascular smooth muscle cells, Cx43, is transcriptionally upregulated by hypoxia and stretch, which surprisingly appears to be mediated by the formation of reactive oxygen species (ROS).