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Nat. Commun., 8, Article number: 15296 (2017) | doi:10.1038/ncomms15296
Plastic roles of pericytes in the blood–retinal barrier
Do Young Park1, Junyeop Lee1, Jaeryung Kim1, Kangsan Kim2, Seonpyo Hong1, Sangyeul Han2, Yoshiaki Kubota3, Hellmut G. Augustin4, Lei Ding5, Jin Woo Kim6, Hail Kim1, Yulong He7, Ralf H. Adams8 & Gou Young Koh1,2,*
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea. 2 Center for Vascular Research, Institute of Basic Science (IBS), Daejeon 34141, Korea. 3The Laboratory of Vascular Biology, Keio University, Tokyo 160-8582, Japan. 4Division of Vascular Oncology and Metastasis, German Cancer Research Center, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. 5 Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York 10032, USA. 6Department of Biological Sciences, KAIST, Daejeon 34141, Korea. 7 Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215123, China. 8Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, and Faculty of Medicine, University of Mu¨nster, D-48149 Mu¨nster, Germany.
*Correspondence and requests for materials should be addressed to G.Y.K..
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea. 2 Center for Vascular Research, Institute of Basic Science (IBS), Daejeon 34141, Korea. 3The Laboratory of Vascular Biology, Keio University, Tokyo 160-8582, Japan. 4Division of Vascular Oncology and Metastasis, German Cancer Research Center, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. 5 Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York 10032, USA. 6Department of Biological Sciences, KAIST, Daejeon 34141, Korea. 7 Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215123, China. 8Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, and Faculty of Medicine, University of Mu¨nster, D-48149 Mu¨nster, Germany.
*Correspondence and requests for materials should be addressed to G.Y.K..
Abstract
The 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.
논문정보
- Research article
- 2017년 05월 (BRIC 등록일 2017-05-23)
- 국내(교신)+국외 연구진
- 의약학 > 재생의학
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