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 journalArticle

14 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 languageEnglish
Pages (from-to)2260-2269
Number of pages10
JournalJournal of Investigative Dermatology
Volume137
Issue number11
DOIs
Publication statusPublished - 2017 Nov 1

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Catenins
Hair Follicle
Wnt Signaling Pathway
Hair
Peptides
Wounds and Injuries
Glycogen Synthase Kinase 3
Cell proliferation
Valproic Acid
Zinc Fingers
Alopecia
Alkaline Phosphatase
Muscle
Zinc
Scalp
Regeneration
Cell Proliferation
Muscles
Skin
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Lee, Soung Hoon ; Seo, Seol Hwa ; Lee, Dong Hwan ; Pi, Long Quan ; Lee, Won Soo ; Choi, Kang-Yell. / Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis. In: Journal of Investigative Dermatology. 2017 ; Vol. 137, No. 11. pp. 2260-2269.
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Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis. / Lee, Soung Hoon; Seo, Seol Hwa; Lee, Dong Hwan; Pi, Long Quan; Lee, Won Soo; Choi, Kang-Yell.

In: Journal of Investigative Dermatology, Vol. 137, No. 11, 01.11.2017, p. 2260-2269.

Research output: Contribution to journalArticle

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AU - Choi, Kang-Yell

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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.

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