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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number38445
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Dec 5 2016

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CD147 Antigens
Retinal Vessels
Diabetic Retinopathy
Claudin-5
Cytokines
Blood Vessels
Endothelial Cells
Caveolin 1
Capillary Permeability
Therapeutics
Streptozocin
Interleukin-1
Vascular Endothelial Growth Factor A
Retina
Cell Membrane
Technology
Injections

All Science Journal Classification (ASJC) codes

  • General

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Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy. / Arima, Mitsuru; Cui, Dan; Kimura, Tokuhiro; Sonoda, Koh Hei; Ishibashi, Tatsuro; Matsuda, Satoshi; Ikeda, Eiji.

In: Scientific reports, Vol. 6, 38445, 05.12.2016.

Research output: Contribution to journalArticle

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