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Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway
DC Field | Value | Language |
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dc.contributor.author | Park, Wonjin | - |
dc.contributor.author | Baek, Yi-Yong | - |
dc.contributor.author | Kim, Joohwan | - |
dc.contributor.author | Jo, Dong Hyun | - |
dc.contributor.author | Choi, Seunghwan | - |
dc.contributor.author | Kim, Jin Hyoung | - |
dc.contributor.author | Kim, Taesam | - |
dc.contributor.author | Kim, Suji | - |
dc.contributor.author | Park, Minsik | - |
dc.contributor.author | Kim, Ji Yoon | - |
dc.contributor.author | Won, Moo-Ho | - |
dc.contributor.author | Ha, Kwon-Soo | - |
dc.contributor.author | Kim, Jeong Hun | - |
dc.contributor.author | Kwon, Young-Guen | - |
dc.contributor.author | Kim, Young-Myeong | - |
dc.date.accessioned | 2023-04-25T07:31:28Z | - |
dc.date.available | 2023-04-25T07:31:28Z | - |
dc.date.created | 2019-11-28 | - |
dc.date.created | 2019-11-28 | - |
dc.date.issued | 2019-09 | - |
dc.identifier.citation | Biomolecules & Therapeutics, Vol.27 No.5, pp.474-483 | - |
dc.identifier.issn | 1976-9148 | - |
dc.identifier.uri | https://hdl.handle.net/10371/191498 | - |
dc.description.abstract | Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGFA-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, beta-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected R LYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that R LYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis. | - |
dc.language | 영어 | - |
dc.publisher | 한국응용약물학회 | - |
dc.title | Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway | - |
dc.type | Article | - |
dc.identifier.doi | 10.4062/biomolther.2019.041 | - |
dc.citation.journaltitle | Biomolecules & Therapeutics | - |
dc.identifier.wosid | 000483952800007 | - |
dc.identifier.scopusid | 2-s2.0-85068845436 | - |
dc.citation.endpage | 483 | - |
dc.citation.number | 5 | - |
dc.citation.startpage | 474 | - |
dc.citation.volume | 27 | - |
dc.identifier.kciid | ART002496012 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Jo, Dong Hyun | - |
dc.contributor.affiliatedAuthor | Kim, Jeong Hun | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | GROWTH-FACTOR | - |
dc.subject.keywordPlus | MACULAR DEGENERATION | - |
dc.subject.keywordPlus | VASCULAR-PERMEABILITY | - |
dc.subject.keywordPlus | DIABETIC-RETINOPATHY | - |
dc.subject.keywordPlus | BASIC SCIENCE | - |
dc.subject.keywordPlus | ANGIOGENESIS | - |
dc.subject.keywordPlus | BEVACIZUMAB | - |
dc.subject.keywordPlus | RANIBIZUMAB | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | MODEL | - |
dc.subject.keywordAuthor | VEGF | - |
dc.subject.keywordAuthor | VEGFR2 | - |
dc.subject.keywordAuthor | Choroidal neovascularization | - |
dc.subject.keywordAuthor | Macular degeneration | - |
dc.subject.keywordAuthor | Vascular leakage | - |
dc.subject.keywordAuthor | Permeability | - |
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