Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy

Mitsuru Arima, Dan Cui, Tokuhiro Kimura, Koh Hei Sonoda, Tatsuro Ishibashi, Satoshi Matsuda, Eiji Ikeda

研究成果: ジャーナルへの寄稿記事

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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.

元の言語英語
記事番号38445
ジャーナルScientific reports
6
DOI
出版物ステータス出版済み - 12 5 2016

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All Science Journal Classification (ASJC) codes

  • General

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