The role of occludin in vascular barrier function in vivo: do we need to re-examine?
The role of occludin in vascular barrier function in vivo: do we need to re-examine?
复制标题
occludin在体内血管屏障功能中的作用：我们需要重新审视吗？
DOI：
10.1186/s13054-020-03178-w
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发表时间：
2020-07
期刊：
影响因子：
15.1
通讯作者：
Tang Yaoqing
中科院分区：
文献类型：
--
作者：
Zhang Ruyuan;Liu Yiyun;Chen Dechang;Tang Yaoqing
亲爱的编辑，脓毒症患者往往会经历精神状态的改变。这种脑功能障碍的一个可能原因被认为与全身炎症引起的血管渗漏有关。Erikson et al.的最新文章[1]结果显示，脓毒症脑组织中主要紧密连接蛋白occludin表达下调，且occludin表达下调与严重的器官功能障碍和全身炎症反应有关.虽然这些发现是新颖和客观的，但我们认为在这项研究和其他相关研究中，将occludin表达减少与血脑屏障功能障碍等同起来可能需要谨慎解释数据。自从紧密连接领域的先驱Shoichiro Tsukita发现它以来，文献中关于occludin在屏障功能中的因果作用的大多数数据都来自体外实验。然而，闭合蛋白缺陷小鼠并没有表现出屏障功能的干扰，具有复杂的病理生理学和无法解释的表型[2]，这甚至使其发现者Shoichiro Tsukita失望。此外，关于闭合蛋白的体内屏障功能的报道很少，主要集中在上皮细胞[3]。令人惊讶的是，查尔斯·M。赖斯的实验室表明，occludin作为丙型肝炎病毒的进入因子[4]，因此赢得了2016年阿尔伯特·拉斯克奖。在另一份最近专门纪念Shoichiro Tsukita博士的报告中，小鼠中occludin缺乏会导致耳聋，同时不会影响紧密连接结构或屏障[5]，因此，由于缺乏occludin缺乏小鼠的血管屏障破坏对于那些研究occludin在体内血管屏障功能中的作用的人和那些使用occludin表达作为血脑屏障功能的指标更可靠。然而，occludin−/−小鼠可能能够补偿occludin的损失。也不能排除闭合蛋白的水平在正常生理条件下发挥有限的作用，但调节血管对病理生理相关应激源的敏感性。未来需要回答的问题包括：出生后小鼠脑内内皮特异性封闭蛋白敲低是否会导致血管渗漏？闭塞缺陷小鼠对败血症更敏感吗？内皮特异性occludin过表达能否预防或限制体内脓毒症诱导的脑血管渗漏？
Dear editor, Septic patients often undergo altered mental status. One possible reason for this brain dysfunction is thought to be related to vascular leakage caused by systemic inflammation. The recent article by Erikson et al.[1] showed that major tight junctions protein occludin in brain autopsy specimens in sepsis was downregulated and that the downregulation of occludin was related with severe organ dysfunction and systemic inflammation. While these findings are novel and objective, we feel it may be necessary to interpret the data with caution regarding to equating the decrease of occludin expression with blood-brain barrier dysfunction in this and other related research. Since its discovery by Shoichiro Tsukita, a pioneer in the field of tight junction, most of the data in literature about the causal role of occludin in barrier function are from in vitro experiments. However, occludin-deficient mice do not display a perturbation of barrier function, with a complex pathophysiological and inexplicable phenotype [2] which even disappointed its discoverer Shoichiro Tsukita. Moreover, few reports regarding the in vivo barrier function of occludin mainly focused on epithelial cells [3]. Surprisingly, research from Charles M. Rice’s lab showed that occludin acts as a hepatitis C virus entry factor [4] and thus won the 2016 Albert Lasker Award. In another recent report dedicated to the memory of Dr. Shoichiro Tsukita, occludin deficiency in mice causes deafness while not affecting the tight junction structure or barrier [5].Therefore, due to the lack of vascular barrier disruption in occludin-deficient mice, additional in vivo animal experiments may be needed to make the conclusions for those studying the role of occludin in vascular barrier function in vivo and those using occludin expression as an indicator of blood-brain barrier function more reliable. However, there is a possibility that occludin−/− mice may be able to compensate for occludin loss. It also cannot be excluded that the level of occludin plays limited roles under normal physiological conditions but modulates the sensitivity of blood vessels to pathophysiologically relevant stressors. Some questions that need to be answered in the future include the following: Will postnatal endothelial-specific occludin knockdown in mouse brain lead to vascular leak? Are occludindeficient mice more sensitive to sepsis? Will endothelial-specific occludin overexpression prevent or limit sepsis-induced brain vascular leak in vivo?
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影响因子：
5.3
作者：
通讯作者：
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影响因子：
10.7
作者：
通讯作者：
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影响因子：
3.2
作者：
通讯作者：
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DOI：
10.1083/jcb.200902153
发表时间：
2010-04-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Marchiando AM;Shen L;Graham WV;Weber CR;Schwarz BT;Austin JR 2nd;Raleigh DR;Guan Y;Watson AJ;Montrose MH;Turner JR
通讯作者：
Turner JR
DOI：
10.1016/s1084-8045(02)00061-9
发表时间：
2003
期刊：
J. Netw. Comput. Appl.
影响因子：
--
作者：
H. V. D. Togt
通讯作者：
H. V. D. Togt