Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis

Soung Hoon Lee; Seol Hwa Seo; Dong Hwan Lee; Long Quan Pi; Won Soo Lee; Kang Yell Choi

doi:10.1016/j.jid.2017.04.038

Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis

Soung Hoon Lee, Seol Hwa Seo, Dong Hwan Lee, Long Quan Pi, Won Soo Lee, Kang Yell Choi

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair regrowth and wound-induced hair follicle neogenesis via an interaction with Dishevelled. CXXC5 was upregulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells. Moreover, CXXC5^−/− mice displayed accelerated hair regrowth, and treatment with valproic acid, a glycogen synthase kinase 3β inhibitor that activates the Wnt/β-catenin pathway, further induced hair regrowth in the CXXC5^−/− mice. Disrupting the CXXC5-Dishevelled interaction with a competitor peptide activated the Wnt/β-catenin pathway and accelerated hair regrowth and wound-induced hair follicle neogenesis. Overall, these findings suggest that the CXXC5-Dishevelled interaction is a potential target for the treatment of hair loss.

Original language	English
Pages (from-to)	2260-2269
Number of pages	10
Journal	Journal of Investigative Dermatology
Volume	137
Issue number	11
DOIs	https://doi.org/10.1016/j.jid.2017.04.038
Publication status	Published - 2017 Nov

Bibliographical note

Funding Information:
We thank the Handok Pharmaceuticals for invaluable suggestions and discussion. This work was supported by grants from the National Research Foundation, the Ministry of Future Creation and Science of Korea through the Translational Research Center for Protein Function Control (2016R1A5A1004694), Mid-Career Researcher Program National Leading Research Lab (2015R1A2A1A05001873). S-HL and SHS were supported by a BK21 PLUS program. These funding sources played no role in the design of the experiments, data collection, data analysis, data interpretation, or the preparation and submission of this manuscript.

Publisher Copyright:
© 2017 The Authors

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology
Dermatology
Cell Biology

Access to Document

10.1016/j.jid.2017.04.038

Cite this

@article{35b135e653204cd7b42f8cf59f9c6365,

title = "Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis",

abstract = "The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair regrowth and wound-induced hair follicle neogenesis via an interaction with Dishevelled. CXXC5 was upregulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells. Moreover, CXXC5−/− mice displayed accelerated hair regrowth, and treatment with valproic acid, a glycogen synthase kinase 3β inhibitor that activates the Wnt/β-catenin pathway, further induced hair regrowth in the CXXC5−/− mice. Disrupting the CXXC5-Dishevelled interaction with a competitor peptide activated the Wnt/β-catenin pathway and accelerated hair regrowth and wound-induced hair follicle neogenesis. Overall, these findings suggest that the CXXC5-Dishevelled interaction is a potential target for the treatment of hair loss.",

author = "Lee, {Soung Hoon} and Seo, {Seol Hwa} and Lee, {Dong Hwan} and Pi, {Long Quan} and Lee, {Won Soo} and Choi, {Kang Yell}",

note = "Funding Information: We thank the Handok Pharmaceuticals for invaluable suggestions and discussion. This work was supported by grants from the National Research Foundation, the Ministry of Future Creation and Science of Korea through the Translational Research Center for Protein Function Control (2016R1A5A1004694), Mid-Career Researcher Program National Leading Research Lab (2015R1A2A1A05001873). S-HL and SHS were supported by a BK21 PLUS program. These funding sources played no role in the design of the experiments, data collection, data analysis, data interpretation, or the preparation and submission of this manuscript. Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = nov,

doi = "10.1016/j.jid.2017.04.038",

language = "English",

volume = "137",

pages = "2260--2269",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis

AU - Lee, Soung Hoon

AU - Seo, Seol Hwa

AU - Lee, Dong Hwan

AU - Pi, Long Quan

AU - Lee, Won Soo

AU - Choi, Kang Yell

N1 - Funding Information: We thank the Handok Pharmaceuticals for invaluable suggestions and discussion. This work was supported by grants from the National Research Foundation, the Ministry of Future Creation and Science of Korea through the Translational Research Center for Protein Function Control (2016R1A5A1004694), Mid-Career Researcher Program National Leading Research Lab (2015R1A2A1A05001873). S-HL and SHS were supported by a BK21 PLUS program. These funding sources played no role in the design of the experiments, data collection, data analysis, data interpretation, or the preparation and submission of this manuscript. Publisher Copyright: © 2017 The Authors

PY - 2017/11

Y1 - 2017/11

N2 - The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair regrowth and wound-induced hair follicle neogenesis via an interaction with Dishevelled. CXXC5 was upregulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells. Moreover, CXXC5−/− mice displayed accelerated hair regrowth, and treatment with valproic acid, a glycogen synthase kinase 3β inhibitor that activates the Wnt/β-catenin pathway, further induced hair regrowth in the CXXC5−/− mice. Disrupting the CXXC5-Dishevelled interaction with a competitor peptide activated the Wnt/β-catenin pathway and accelerated hair regrowth and wound-induced hair follicle neogenesis. Overall, these findings suggest that the CXXC5-Dishevelled interaction is a potential target for the treatment of hair loss.

AB - The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair regrowth and wound-induced hair follicle neogenesis via an interaction with Dishevelled. CXXC5 was upregulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells. Moreover, CXXC5−/− mice displayed accelerated hair regrowth, and treatment with valproic acid, a glycogen synthase kinase 3β inhibitor that activates the Wnt/β-catenin pathway, further induced hair regrowth in the CXXC5−/− mice. Disrupting the CXXC5-Dishevelled interaction with a competitor peptide activated the Wnt/β-catenin pathway and accelerated hair regrowth and wound-induced hair follicle neogenesis. Overall, these findings suggest that the CXXC5-Dishevelled interaction is a potential target for the treatment of hair loss.

UR - http://www.scopus.com/inward/record.url?scp=85031995249&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031995249&partnerID=8YFLogxK

U2 - 10.1016/j.jid.2017.04.038

DO - 10.1016/j.jid.2017.04.038

M3 - Article

C2 - 28595998

AN - SCOPUS:85031995249

SN - 0022-202X

VL - 137

SP - 2260

EP - 2269

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 11

ER -

Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this