Cited 49 times in
The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김희수 | - |
dc.contributor.author | 노미령 | - |
dc.contributor.author | 정기양 | - |
dc.date.accessioned | 2016-02-04T11:31:13Z | - |
dc.date.available | 2016-02-04T11:31:13Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/140609 | - |
dc.description.abstract | Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of β-catenin, α-smooth muscle actin (α-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5(-/-) mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)-Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated β-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor which activates the Wnt/β-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 1061~1080 | - |
dc.relation.isPartOf | JOURNAL OF EXPERIMENTAL MEDICINE | - |
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 | Actins/metabolism | - |
dc.subject.MESH | Adaptor Proteins, Signal Transducing/metabolism* | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Blotting, Western | - |
dc.subject.MESH | Collagen/metabolism | - |
dc.subject.MESH | DNA Primers/genetics | - |
dc.subject.MESH | Dishevelled Proteins | - |
dc.subject.MESH | Fibroblasts/metabolism | - |
dc.subject.MESH | Galactosides | - |
dc.subject.MESH | Histological Techniques | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunohistochemistry | - |
dc.subject.MESH | Immunoprecipitation | - |
dc.subject.MESH | Indoles | - |
dc.subject.MESH | Intracellular Signaling Peptides and Proteins/genetics | - |
dc.subject.MESH | Intracellular Signaling Peptides and Proteins/metabolism* | - |
dc.subject.MESH | Keratin-14/metabolism | - |
dc.subject.MESH | Keratinocytes/metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Knockout | - |
dc.subject.MESH | Phosphoproteins/metabolism* | - |
dc.subject.MESH | Reverse Transcriptase Polymerase Chain Reaction | - |
dc.subject.MESH | Skin Physiological Phenomena* | - |
dc.subject.MESH | Wnt Signaling Pathway/physiology* | - |
dc.subject.MESH | Wound Healing/physiology* | - |
dc.subject.MESH | beta Catenin/metabolism | - |
dc.title | The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Dermatology (피부과학) | - |
dc.contributor.googleauthor | Soung Hoon Lee | - |
dc.contributor.googleauthor | Mi Yeon Kim | - |
dc.contributor.googleauthor | Hyun Yi Kim | - |
dc.contributor.googleauthor | Young Mi Lee | - |
dc.contributor.googleauthor | Heesu Kim | - |
dc.contributor.googleauthor | Kyoung Ae Nam | - |
dc.contributor.googleauthor | Mi Ryung Roh | - |
dc.contributor.googleauthor | Do Sik Min | - |
dc.contributor.googleauthor | Kee Yang Chung | - |
dc.contributor.googleauthor | Kang Yell Choi | - |
dc.identifier.doi | 10.1084/jem.20141601 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01211 | - |
dc.contributor.localId | A01278 | - |
dc.contributor.localId | A03582 | - |
dc.relation.journalcode | J01409 | - |
dc.identifier.eissn | 1540-9538 | - |
dc.identifier.pmid | 26056233 | - |
dc.identifier.url | http://jem.rupress.org/content/212/7/1061 | - |
dc.contributor.alternativeName | Kim, Hee Su | - |
dc.contributor.alternativeName | Roh, Mi Ryung | - |
dc.contributor.alternativeName | Chung, Kee Yang | - |
dc.contributor.affiliatedAuthor | Kim, Hee Su | - |
dc.contributor.affiliatedAuthor | Roh, Mi Ryung | - |
dc.contributor.affiliatedAuthor | Chung, Kee Yang | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 212 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 1061 | - |
dc.citation.endPage | 1080 | - |
dc.identifier.bibliographicCitation | JOURNAL OF EXPERIMENTAL MEDICINE, Vol.212(7) : 1061-1080, 2015 | - |
dc.identifier.rimsid | 30203 | - |
dc.type.rims | ART | - |
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