Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy.
Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy.
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DOI：
10.1038/srep38445
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发表时间：
2016-12-05
影响因子：
4.6
通讯作者：
Ikeda E
中科院分区：
文献类型：
--
作者：
Arima M;Cui D;Kimura T;Sonoda KH;Ishibashi T;Matsuda S;Ikeda E
尽管医学技术不断进步，但糖尿病性视网膜病变（DR）仍然是一种顽固性疾病，它导致视网膜细胞损伤，最终导致视力丧失。多种炎症细胞因子混合引发的视网膜血管屏障损伤是dr的病理生理学核心，因此，与多种细胞因子诱导的血管屏障损伤相关的分子将成为dr的根治性治疗目标。是血管屏障损伤所必需的分子，它由多种触发因素共享，包括VEGF、TNFα和IL-1β。神经微血管内皮细胞的体外数据表明，细胞因子的刺激降低了细胞膜中claudin-5的水平，从而以依赖于claudin-5与basigin和caveolin-1相互作用的方式损害了屏障功能。此外，在链脲佐菌素诱导的糖尿病小鼠视网膜血管通透性增加的情况下，通过玻璃体内注射basigin特异性sirna被证明明显正常化。本研究强调了盆子碱是各种刺激引起的视网膜血管屏障损伤的共同必需分子，可以作为建立DR根治性治疗策略的靶点。
Despite the advance in medical technology, diabetic retinopathy (DR) is still an intractable disease which leads to the damage of retinal cells and finally the visual loss. Impairment of retinal vascular barrier triggered by an admixture of multiple inflammatory cytokines is a core of pathophysiology of DR. Therefore, the molecules involved commonly in multiple cytokines-induced impairment of vascular barrier would be the targets of curative treatment of DR. Here, we demonstrate that basigin, a transmembrane molecule expressed in neural barrier-forming endothelial cells, is the molecule essential for vascular barrier impairment which is shared by various triggers including VEGF, TNFα and IL-1β. In vitro data with neural microvascular endothelial cells indicated that stimulation with cytokines decreases the levels of claudin-5 in cell membranes and consequently impairs the barrier function in a manner dependent on the interaction of claudin-5 with basigin and caveolin-1. In addition, the increased vascular permeability in retinas of streptozotocin-induced diabetic mice was shown to be clearly normalized by intravitreous injection of siRNAs specific for basigin. This study has highlighted basigin as a common essential molecule for various stimuli-induced impairment of retinal vascular barrier, which can be a target for strategies to establish a curative treatment of DR.
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