Increased caveolin-1 expression precedes decreased expression of occludin and claudin-5 during blood-brain barrier breakdown
Increased caveolin-1 expression precedes decreased expression of occludin and claudin-5 during blood-brain barrier breakdown
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DOI：
10.1007/s00401-007-0274-x
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发表时间：
2007-11-01
影响因子：
12.7
通讯作者：
Stewart, Duncan J.
中科院分区：
文献类型：
--
作者：
Nag, Sukriti;Venugopalan, Roopa;Stewart, Duncan J.
小窝蛋白-1，小窝的主要组成部分，和紧密连接蛋白occludin和claudin-5在早期血脑屏障（BBB）的崩溃的意义进行了评估，这些蛋白质的表达在一段时间内的连续演示损伤后12小时至6天在大鼠皮层冷损伤模型。对照组大鼠软膜和脑内血管呈点状内皮细胞caveolin-1和caveolin-2免疫反应阳性，而claudin-5和occludin定位为内皮细胞中的纵向链。在损伤后12 h和第2天BBB破裂的早期阶段，蛋白质印迹分析检测到损伤部位的小窝蛋白-1表达显著增加，而免疫组化显示小窝蛋白-1的增加定位于损伤血管的内皮。occludin的表达减少发生在病变部位仅在病变后第2天和第4天，而claudin-5的表达仅在第2天减少。纤连蛋白（BBB破裂的标志物）和小窝蛋白-1或紧密连接蛋白的双重标记表明，只有BBB破裂的病变血管显示小窝蛋白-1显著增加，封闭蛋白丢失和封闭蛋白-5的定位减少。这些改变是在BBB破裂之前还是之后的问题尚不确定;然而，窖蛋白-1的表达增加先于闭合蛋白和密蛋白-5的表达减少。因此，小窝和小窝蛋白-1在早期BBB破坏中具有重要作用，并且可能是控制早期脑水肿的潜在治疗靶点。
The significance of caveolin-1, a major constituent of caveolae, and the tight junction proteins occludin and claudin-5 in early blood-brain barrier (BBB) breakdown was assessed by sequential demonstration of the expression of these proteins over a period of 12 h to 6 days post-lesion in the rat cortical cold injury model. Pial and intracerebral vessels of control rats showed punctuate endothelial immunoreactivity for caveolin-1 and caveolin-2, while claudin-5 and occludin were localized as longitudinal strands in endothelium. During the early phase of BBB breakdown following injury at 12 h and on day 2, western blot analyses detected a significant increase in caveolin-1 expression at the lesion site while immunohistochemistry showed that the caveolin-1 increase was localized to the endothelium of lesion vessels. Decreased expression of occludin occurred at the lesion site only on days 2 and 4 post-lesion while claudin-5 expression was decreased only on day 2. Dual labeling for fibronectin, a marker of BBB breakdown, and caveolin-1 or the tight junction proteins demonstrated that only lesion vessels with BBB breakdown showed a marked increase of caveolin-1, loss of occludin and reduced localization of claudin-5. The issue whether these alterations precede or follow BBB breakdown is uncertain; however, increased expression of caveolin-1 preceded the decreased expression of occludin and claudin-5. Thus caveolae and caveolin-1 have an important role in early BBB breakdown and could be potential therapeutic targets in the control of early brain edema.