{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:35:26Z","timestamp":1790357726371,"version":"4.1.0"},"reference-count":50,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,6,29]]},"abstract":"<jats:p>Wnt\/\u03b2-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\/\u03b2-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 \u03b2-catenin, \u03b1-smooth muscle actin (\u03b1-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\u2212\/\u2212 mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)\u2013Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated \u03b2-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3\u03b2 (GSK3\u03b2) inhibitor which activates the Wnt\/\u03b2-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.<\/jats:p>","DOI":"10.1084\/jem.20141601","type":"journal-article","created":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T15:44:50Z","timestamp":1433951090000},"page":"1061-1080","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":58,"title":["The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing"],"prefix":"10.1084","volume":"212","author":[{"given":"Soung-Hoon","family":"Lee","sequence":"first","affiliation":[{"name":"Translational Research Center for Protein Function Control 1 ; 2 ; and 3"},{"name":"Department of Biotechnology, College of Life Science and Biotechnology 1 ; 2 ; and 3"},{"name":"Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, College of Medicine; Yonsei University, Seoul 120-749, South Korea 1 ; 2 ; and 3"},{"name":"Translational Research Center for Protein Function Control 1 ; 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