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Gemigliptin, a dipeptidyl peptidase-4 inhibitor, inhibits retinal pericyte injury in db/db mice and retinal neovascularization in mice with ischemic retinopathy
DC Field | Value | Language |
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dc.contributor.author | Jung, Eunsoo | - |
dc.contributor.author | Kim, Junghyun | - |
dc.contributor.author | Kim, Chan-Sik | - |
dc.contributor.author | Kim, Sung-Ho | - |
dc.contributor.author | Cho, Myung-Haing | - |
dc.date.accessioned | 2021-01-31T08:39:35Z | - |
dc.date.available | 2021-01-31T08:39:35Z | - |
dc.date.created | 2018-10-10 | - |
dc.date.issued | 2015-12 | - |
dc.identifier.citation | Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol.1852 No.12, pp.2618-2629 | - |
dc.identifier.issn | 0925-4439 | - |
dc.identifier.other | 59117 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172327 | - |
dc.description.abstract | Retinal pericyte loss and neovascularization are characteristic features of diabetic retinopathy. Gemigliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has shown robust blood-glucose lowering effects in type 2 diabetic patients, but its effects on diabetic retinopathy have not yet been reported. We evaluated the efficacy of gemigliptin on retinal vascular leakage in db/db mice, which is an animal model for type 2 diabetes, and neovascularization in oxygen-induced retinopathy (OIR) mice, which is an animal model for ischemic proliferative retinopathy. Gemigliptin (100 mg/kg/day) was orally administered to the db/db mice for 12 weeks. C57BL/6 mice on postnatal day 7 (P7) were exposed to 75% hyperoxia for 5 days, followed by exposure to room air from P12 to P17 to induce OIR. Gemigliptin (50 mg/kg/day) was intraperitoneally injected daily from P12 to P17. Retinal neovascularization was analyzed in flat-mounted retinas on P17. We determined the efficacy and possible mechanism of gemigliptin on high glucose-induced apoptosis of primary human retinal pericytes. The oral administration of gemigliptin for 4 months significantly ameliorated retinal pericyte apoptosis and vascular leakage in the db/db mice. Gemigliptin also ameliorated retinal neovascularization in the OIR mice. Gemigliptin attenuated the overexpression of plasminogen activator inhibitor-1 (PAM) in the retinas of diabetic and OIR mice. Gemigliptin and PAI-1 siRNA significantly inhibited pericyte apoptosis by inhibiting the overexpression of PAI-1, which is induced by high glucose. Our results suggest that gemigliptin has potent anti-angiogenic and anti-apoptotic activities via suppressing DPP-4 and PAI-1, and the results support the direct retinoprotective action of gemigliptin. (C) 2015 Elsevier B.V. All rights reserved. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier BV | - |
dc.title | Gemigliptin, a dipeptidyl peptidase-4 inhibitor, inhibits retinal pericyte injury in db/db mice and retinal neovascularization in mice with ischemic retinopathy | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 조명행 | - |
dc.identifier.doi | 10.1016/j.bbadis.2015.09.010 | - |
dc.citation.journaltitle | Biochimica et Biophysica Acta - Molecular Basis of Disease | - |
dc.identifier.wosid | 000363827300006 | - |
dc.identifier.scopusid | 2-s2.0-84942645634 | - |
dc.citation.endpage | 2629 | - |
dc.citation.number | 12 | - |
dc.citation.startpage | 2618 | - |
dc.citation.volume | 1852 | - |
dc.identifier.sci | 000363827300006 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Cho, Myung-Haing | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | PLASMINOGEN-ACTIVATOR INHIBITOR-1 | - |
dc.subject.keywordPlus | OXYGEN-INDUCED RETINOPATHY | - |
dc.subject.keywordPlus | DIABETIC-RETINOPATHY | - |
dc.subject.keywordPlus | ENDOTHELIAL-CELLS | - |
dc.subject.keywordPlus | BARRIER BREAKDOWN | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | TYPE-1 | - |
dc.subject.keywordPlus | OVEREXPRESSION | - |
dc.subject.keywordPlus | QUANTIFICATION | - |
dc.subject.keywordAuthor | Diabetic retinopathy | - |
dc.subject.keywordAuthor | Gemigliptin | - |
dc.subject.keywordAuthor | Neovascularization | - |
dc.subject.keywordAuthor | Pericyte | - |
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