Cited 87 times in
The WNT antagonist Dickkopf2 promotes angiogenesis in rodent and human endothelial cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 송병욱 | - |
dc.contributor.author | 윤채옥 | - |
dc.contributor.author | 황기철 | - |
dc.date.accessioned | 2014-12-20T16:51:16Z | - |
dc.date.available | 2014-12-20T16:51:16Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/93504 | - |
dc.description.abstract | Neovessel 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 Dickkopf1 (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 LRP6-mediated APC/Asef2/Cdc42 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.description.statementOfResponsibility | open | - |
dc.format.extent | 1882~1893 | - |
dc.relation.isPartOf | JOURNAL OF CLINICAL INVESTIGATION | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Aorta/metabolism | - |
dc.subject.MESH | Endothelial Cells/cytology* | - |
dc.subject.MESH | Gene Expression Regulation* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Intercellular Signaling Peptides and Proteins/metabolism* | - |
dc.subject.MESH | Ischemia/pathology | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Myocardial Infarction/pathology | - |
dc.subject.MESH | Neovascularization, Pathologic* | - |
dc.subject.MESH | Proteins/metabolism* | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Rats, Sprague-Dawley | - |
dc.subject.MESH | Umbilical Cord/cytology | - |
dc.subject.MESH | Wnt Proteins/metabolism* | - |
dc.title | The WNT antagonist Dickkopf2 promotes angiogenesis in rodent and human endothelial cells | - |
dc.type | Article | - |
dc.contributor.college | Researcher Institutes (부설 연구소) | - |
dc.contributor.department | Institute for Cancer Research (암연구소) | - |
dc.contributor.googleauthor | Jeong-Ki Min | - |
dc.contributor.googleauthor | Hongryeol Park | - |
dc.contributor.googleauthor | Hyun-Jung Choi | - |
dc.contributor.googleauthor | Yonghak Kim | - |
dc.contributor.googleauthor | Bo-Jeong Pyun | - |
dc.contributor.googleauthor | Vijayendra Agrawal | - |
dc.contributor.googleauthor | Byeong-Wook Song | - |
dc.contributor.googleauthor | Jongwook Jeon | - |
dc.contributor.googleauthor | Yong-Sun Maeng | - |
dc.contributor.googleauthor | Seung-Sik Rho | - |
dc.contributor.googleauthor | Sungbo Shim | - |
dc.contributor.googleauthor | Jin-Ho Chai | - |
dc.contributor.googleauthor | Bon-Kyoung Koo | - |
dc.contributor.googleauthor | Hyo Jeong Hong | - |
dc.contributor.googleauthor | Chae-Ok Yun | - |
dc.contributor.googleauthor | Chulhee Choi | - |
dc.contributor.googleauthor | Young-Myoung Kim | - |
dc.contributor.googleauthor | Ki-Chul Hwang | - |
dc.contributor.googleauthor | Young-Guen Kwon | - |
dc.identifier.doi | 10.1172/JCI42556 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A02026 | - |
dc.contributor.localId | A02614 | - |
dc.contributor.localId | A04456 | - |
dc.relation.journalcode | J01322 | - |
dc.identifier.eissn | 1558-8238 | - |
dc.identifier.pmid | 21540552 | - |
dc.contributor.alternativeName | Song, Byeong Wook | - |
dc.contributor.alternativeName | Yun, Chae Ok | - |
dc.contributor.alternativeName | Hwang, Ki Chul | - |
dc.contributor.affiliatedAuthor | Song, Byeong Wook | - |
dc.contributor.affiliatedAuthor | Yun, Chae Ok | - |
dc.contributor.affiliatedAuthor | Hwang, Ki Chul | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 121 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 1882 | - |
dc.citation.endPage | 1893 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CLINICAL INVESTIGATION, Vol.121(5) : 1882-1893, 2011 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.