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The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing

Title
 The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing
Authors
 Soung Hoon Lee; Mi Yeon Kim; Kang Yell Choi; Kee Yang Chung; Do Sik Min; Mi Ryung Roh; Kyoung Ae Nam; Heesu Kim; Young Mi Lee; Hyun Yi Kim
Issue Date
2015
Journal Title
 Journal of Experimental Medicine
ISSN
 0022-1007
Citation
 Journal of Experimental Medicine, Vol.212(7) : 1061~1080, 2015
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/140609
DOI
10.1084/jem.20141601
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Dermatology
Yonsei Authors
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Link
 http://jem.rupress.org/content/212/7/1061
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