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The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing

DC Field Value Language
dc.contributor.author김희수-
dc.contributor.author노미령-
dc.contributor.author정기양-
dc.date.accessioned2016-02-04T11:31:13Z-
dc.date.available2016-02-04T11:31:13Z-
dc.date.issued2015-
dc.identifier.issn0022-1007-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/140609-
dc.description.abstractWnt/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.statementOfResponsibilityopen-
dc.format.extent1061~1080-
dc.relation.isPartOfJOURNAL OF EXPERIMENTAL MEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHActins/metabolism-
dc.subject.MESHAdaptor Proteins, Signal Transducing/metabolism*-
dc.subject.MESHAnimals-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCollagen/metabolism-
dc.subject.MESHDNA Primers/genetics-
dc.subject.MESHDishevelled Proteins-
dc.subject.MESHFibroblasts/metabolism-
dc.subject.MESHGalactosides-
dc.subject.MESHHistological Techniques-
dc.subject.MESHHumans-
dc.subject.MESHImmunohistochemistry-
dc.subject.MESHImmunoprecipitation-
dc.subject.MESHIndoles-
dc.subject.MESHIntracellular Signaling Peptides and Proteins/genetics-
dc.subject.MESHIntracellular Signaling Peptides and Proteins/metabolism*-
dc.subject.MESHKeratin-14/metabolism-
dc.subject.MESHKeratinocytes/metabolism-
dc.subject.MESHMice-
dc.subject.MESHMice, Knockout-
dc.subject.MESHPhosphoproteins/metabolism*-
dc.subject.MESHReverse Transcriptase Polymerase Chain Reaction-
dc.subject.MESHSkin Physiological Phenomena*-
dc.subject.MESHWnt Signaling Pathway/physiology*-
dc.subject.MESHWound Healing/physiology*-
dc.subject.MESHbeta Catenin/metabolism-
dc.titleThe Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Dermatology (피부과학)-
dc.contributor.googleauthorSoung Hoon Lee-
dc.contributor.googleauthorMi Yeon Kim-
dc.contributor.googleauthorHyun Yi Kim-
dc.contributor.googleauthorYoung Mi Lee-
dc.contributor.googleauthorHeesu Kim-
dc.contributor.googleauthorKyoung Ae Nam-
dc.contributor.googleauthorMi Ryung Roh-
dc.contributor.googleauthorDo Sik Min-
dc.contributor.googleauthorKee Yang Chung-
dc.contributor.googleauthorKang Yell Choi-
dc.identifier.doi10.1084/jem.20141601-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01211-
dc.contributor.localIdA01278-
dc.contributor.localIdA03582-
dc.relation.journalcodeJ01409-
dc.identifier.eissn1540-9538-
dc.identifier.pmid26056233-
dc.identifier.urlhttp://jem.rupress.org/content/212/7/1061-
dc.contributor.alternativeNameKim, Hee Su-
dc.contributor.alternativeNameRoh, Mi Ryung-
dc.contributor.alternativeNameChung, Kee Yang-
dc.contributor.affiliatedAuthorKim, Hee Su-
dc.contributor.affiliatedAuthorRoh, Mi Ryung-
dc.contributor.affiliatedAuthorChung, Kee Yang-
dc.rights.accessRightsnot free-
dc.citation.volume212-
dc.citation.number7-
dc.citation.startPage1061-
dc.citation.endPage1080-
dc.identifier.bibliographicCitationJOURNAL OF EXPERIMENTAL MEDICINE, Vol.212(7) : 1061-1080, 2015-
dc.identifier.rimsid30203-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers

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