DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jung, Keehoon | ko |
dc.contributor.author | Lee, Donghun | ko |
dc.contributor.author | Lim, Hye Song | ko |
dc.contributor.author | Lee, Sang-Il | ko |
dc.contributor.author | Kim, Yeon Jung | ko |
dc.contributor.author | Lee, Gyun-Min | ko |
dc.contributor.author | Kim, Sun-Chang | ko |
dc.contributor.author | Koh, Gou Young | ko |
dc.date.accessioned | 2013-03-12T01:31:39Z | - |
dc.date.available | 2013-03-12T01:31:39Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2011-04 | - |
dc.identifier.citation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.286, no.16, pp.14410 - 14418 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10203/100968 | - |
dc.description.abstract | Pathological angiogenesis usually involves disrupted vascular integrity, vascular leakage, and infiltration of inflammatory cells, which are governed mainly by VEGF-A and TNF-alpha. Although many inhibitors targeting either VEGF-A or TNF-alpha have been developed, there is no single inhibitor molecule that simultaneously targets both molecules. Here, we designed and generated a novel chimeric decoy receptor (Valpha) that can simultaneously bind to VEGF-A and TNF-alpha and block their actions. In this experimental design, we have shown that Valpha, which is an effective synchronous blocker of VEGF-A and TNF-alpha, can drastically increase treatment effectiveness through its dual-blocking characteristics. Valpha contains the VEGF-A-binding domain of VEGFR1, the TNF-alpha-binding domain of TNFR2, and the Fc domain of IgG1. Valpha exhibited strong binding characteristics for its original counterparts, VEGF-A and TNF-alpha, but not for the extracellular matrix, resulting in a highly favorable pharmacokinetic profile in vivo. Compared with VEGF-Trap or Enbrel, both of which block either VEGF-A or TNF-alpha, singularly, Valpha is a highly effective molecule for reducing abnormal vascular tufts and the number of F4/80(+) macrophages in a retinopathy model. In addition, Valpha showed superior relief effects in a psoriasis model with regard to epidermal thickness and the area of blood and lymphatic vessels. Thus, the simultaneous blocking of VEGF-A and TNF-alpha using Valpha is an effective therapeutic strategy and cost-efficient for treatment of retinopathy and psoriasis. | - |
dc.language | English | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject | TUMOR-NECROSIS-FACTOR | - |
dc.subject | NF-KAPPA-B | - |
dc.subject | SKIN INFLAMMATION | - |
dc.subject | RHEUMATOID-ARTHRITIS | - |
dc.subject | CANCER MODEL | - |
dc.subject | IN-VIVO | - |
dc.subject | RECEPTOR | - |
dc.subject | MOUSE | - |
dc.subject | NEOVASCULARIZATION | - |
dc.title | Double Anti-angiogenic and Anti-inflammatory Protein Valpha Targeting VEGF-A and TNF-alpha in Retinopathy and Psoriasis | - |
dc.type | Article | - |
dc.identifier.wosid | 000289556200062 | - |
dc.identifier.scopusid | 2-s2.0-79954600126 | - |
dc.type.rims | ART | - |
dc.citation.volume | 286 | - |
dc.citation.issue | 16 | - |
dc.citation.beginningpage | 14410 | - |
dc.citation.endingpage | 14418 | - |
dc.citation.publicationname | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.contributor.localauthor | Lee, Gyun-Min | - |
dc.contributor.localauthor | Kim, Sun-Chang | - |
dc.contributor.localauthor | Koh, Gou Young | - |
dc.contributor.nonIdAuthor | Lee, Donghun | - |
dc.contributor.nonIdAuthor | Lim, Hye Song | - |
dc.contributor.nonIdAuthor | Lee, Sang-Il | - |
dc.contributor.nonIdAuthor | Kim, Yeon Jung | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject.keywordPlus | TUMOR-NECROSIS-FACTOR | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | SKIN INFLAMMATION | - |
dc.subject.keywordPlus | RHEUMATOID-ARTHRITIS | - |
dc.subject.keywordPlus | CANCER MODEL | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | MOUSE | - |
dc.subject.keywordPlus | NEOVASCULARIZATION | - |
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