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000124246 1001_ $$aPark, Do Young$$b0
000124246 245__ $$aPlastic roles of pericytes in the blood-retinal barrier.
000124246 260__ $$aLondon$$bNature Publishing Group$$c2017
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000124246 520__ $$aThe blood-retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption. However, PDGF-B/PDGFRβ signalling is expendable for maintaining BRB integrity in adult mice. Although selective pericyte loss in stable adult retinal vessels surprisingly does not cause BRB disintegration, it sensitizes retinal vascular endothelial cells (ECs) to VEGF-A, leading to upregulation of angiopoietin-2 (Ang2) in ECs through FOXO1 activation and triggering a positive feedback that resembles the pathogenesis of DR. Accordingly, either blocking Ang2 or activating Tie2 greatly attenuates BRB breakdown, suggesting potential therapeutic approaches to reduce retinal damages upon DR progression.
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000124246 7001_ $$aLee, Junyeop$$b1
000124246 7001_ $$aKim, Jaeryung$$b2
000124246 7001_ $$aKim, Kangsan$$b3
000124246 7001_ $$aHong, Seonpyo$$b4
000124246 7001_ $$aHan, Sangyeul$$b5
000124246 7001_ $$aKubota, Yoshiaki$$b6
000124246 7001_ $$00000-0002-7173-4242$$aAugustin, Hellmut G$$b7
000124246 7001_ $$aDing, Lei$$b8
000124246 7001_ $$aKim, Jin Woo$$b9
000124246 7001_ $$aKim, Hail$$b10
000124246 7001_ $$00000-0002-0099-3749$$aHe, Yulong$$b11
000124246 7001_ $$00000-0003-3031-7677$$aAdams, Ralf H$$b12
000124246 7001_ $$00000-0002-1231-1485$$aKoh, Gou Young$$b13
000124246 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/ncomms15296$$gVol. 8, p. 15296 -$$p15296 -$$tNature Communications$$v8$$x2041-1723$$y2017
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