The WNT antagonist Dickkopf2 promotes angiogenesis in rodent and human endothelial cells

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dc.contributor.authorMin, Jeong-Kiko
dc.contributor.authorPark, Hongryeolko
dc.contributor.authorChoi, Hyun-Jungko
dc.contributor.authorKim, Yonghakko
dc.contributor.authorAgrawal, Vijayendrako
dc.contributor.authorSong, Byeong-Wookko
dc.contributor.authorJeon, Jongwookko
dc.contributor.authorMaeng, Yong-Sunko
dc.contributor.authorRho, Seung-Sikko
dc.contributor.authorShim, Sungboko
dc.contributor.authorChai, Jin-Hoko
dc.contributor.authorKoo, Bon-Kyoungko
dc.contributor.authorHong, Hyo Jeongko
dc.contributor.authorYun, Chae-Okko
dc.contributor.authorChoi, Chulheeko
dc.contributor.authorKim, Young-Myoungko
dc.contributor.authorHwang, Ki-Chulko
dc.contributor.authorKwon, Young-Guenko
dc.date.accessioned2013-03-09T18:50:37Z-
dc.date.available2013-03-09T18:50:37Z-
dc.date.created2012-02-06-
dc.date.created2012-02-06-
dc.date.issued2011-05-
dc.identifier.citationJOURNAL OF CLINICAL INVESTIGATION, v.121, no.5, pp.1882 - 1893-
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10203/97194-
dc.description.abstractNeovessel formation is a complex process governed by the orchestrated action of multiple factors that regulate EC specification and dynamics within a growing vascular tree. These factors have been widely exploited to develop therapies for angiogenesis-related diseases such as diabetic retinopathy and tumor growth and metastasis. WNT signaling has been implicated in the regulation and development of the vascular system, but the detailed mechanism of this process remains unclear. Here, we report that Dickkopfl (DKK1) and Dickkopf2 (DKK2), originally known as WNT antagonists, play opposite functional roles in regulating angiogenesis. DKK2 induced during EC morphogenesis promoted angiogenesis in cultured human endothelial cells and in in vivo assays using mice. Its structural homolog, DKK1, suppressed angiogenesis and was repressed upon induction of morphogenesis. Importantly, local injection of DKK2 protein significantly improved tissue repair, with enhanced neovascularization in animal models of both hind limb ischemia and myocardial infarction. We further showed that DKK2 stimulated filopodial dynamics and angiogenic sprouting of ECs via a signaling cascade involving LRP6mediated APC/Asef2/Cd.c42 activation. Thus, our findings demonstrate the distinct functions of DKK1 and DKK2 in controlling angiogenesis and suggest that DKK2 may be a viable therapeutic target in the treatment of ischemic vascular diseases.-
dc.languageEnglish-
dc.publisherAMER SOC CLINICAL INVESTIGATION INC-
dc.subjectGROWTH-FACTOR-
dc.subjectSIGNALING PATHWAY-
dc.subjectVASCULAR MORPHOGENESIS-
dc.subjectHINDLIMB ISCHEMIA-
dc.subjectEXCHANGE FACTOR-
dc.subjectHEAD INDUCTION-
dc.subjectTUMOR-GROWTH-
dc.subjectSTEM-CELLS-
dc.subjectNOTCH-
dc.subjectRECEPTOR-
dc.titleThe WNT antagonist Dickkopf2 promotes angiogenesis in rodent and human endothelial cells-
dc.typeArticle-
dc.identifier.wosid000290246800023-
dc.identifier.scopusid2-s2.0-79955503633-
dc.type.rimsART-
dc.citation.volume121-
dc.citation.issue5-
dc.citation.beginningpage1882-
dc.citation.endingpage1893-
dc.citation.publicationnameJOURNAL OF CLINICAL INVESTIGATION-
dc.identifier.doi10.1172/JCI42556-
dc.contributor.localauthorChoi, Chulhee-
dc.contributor.nonIdAuthorMin, Jeong-Ki-
dc.contributor.nonIdAuthorPark, Hongryeol-
dc.contributor.nonIdAuthorChoi, Hyun-Jung-
dc.contributor.nonIdAuthorKim, Yonghak-
dc.contributor.nonIdAuthorAgrawal, Vijayendra-
dc.contributor.nonIdAuthorSong, Byeong-Wook-
dc.contributor.nonIdAuthorMaeng, Yong-Sun-
dc.contributor.nonIdAuthorRho, Seung-Sik-
dc.contributor.nonIdAuthorShim, Sungbo-
dc.contributor.nonIdAuthorChai, Jin-Ho-
dc.contributor.nonIdAuthorKoo, Bon-Kyoung-
dc.contributor.nonIdAuthorHong, Hyo Jeong-
dc.contributor.nonIdAuthorYun, Chae-Ok-
dc.contributor.nonIdAuthorKim, Young-Myoung-
dc.contributor.nonIdAuthorHwang, Ki-Chul-
dc.contributor.nonIdAuthorKwon, Young-Guen-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusGROWTH-FACTOR-
dc.subject.keywordPlusSIGNALING PATHWAY-
dc.subject.keywordPlusVASCULAR MORPHOGENESIS-
dc.subject.keywordPlusHINDLIMB ISCHEMIA-
dc.subject.keywordPlusEXCHANGE FACTOR-
dc.subject.keywordPlusHEAD INDUCTION-
dc.subject.keywordPlusTUMOR-GROWTH-
dc.subject.keywordPlusSTEM-CELLS-
dc.subject.keywordPlusNOTCH-
dc.subject.keywordPlusRECEPTOR-
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