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KY19382, a novel activator of Wnt/β-catenin signaling, promotes hair re-growth and hair follicle neogenesis
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  • YEONG CHAN RYU,
  • Dong-Hwan Lee,
  • Jiyong Shim,
  • Jiyeon Park,
  • You-rin Kim,
  • Sehee Choi,
  • Soon Sun Bak,
  • Young Kwan Sung,
  • Soung-Hoon Lee,
  • Kang-Yell Choi
YEONG CHAN RYU
Yonsei University
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Dong-Hwan Lee
Yonsei University
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Jiyong Shim
Yonsei University
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Jiyeon Park
Yonsei University
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You-rin Kim
Yonsei University
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Sehee Choi
Yonsei University
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Soon Sun Bak
Kyungpook National University
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Young Kwan Sung
Kyungpook National University
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Soung-Hoon Lee
Yonsei University
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Kang-Yell Choi
Yonsei University
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Abstract

Background and Purpose: The promotion of hair regeneration and growth heavily depends on the activation of Wnt/β-catenin signaling in the hair follicle including dermal papilla (DP). KY19382, one of the newly synthesized analogs of indirubin-3’-monoxime (I3O) was identified as a Wnt/β-catenin signaling activator via inhibition of the interaction between CXXC-type zinc finger protein 5 (CXXC5) and Dishevelled (Dvl) interaction. Given the close relationship between the Wnt/β-catenin signaling and hair regeneration, we investigated the effect of KY19382 on hair re-growth and hair follicle neogenesis. Experimental Approach: In vitro hair induction effects of KY19382 was performed in human dermal papilla cells. The hair elongation effects of KY19382 was confirmed through the vibrissa culture system. In vivo hair regeneration abilities of KY19382 was identified in three models: hair regrowth, wound-induced hair follicle neogenesis (WIHN), and hair patch assays using C57BL/6 mice. The hair regeneration abilities were analyzed by immunoblotting, alkaline phosphatase (ALP) and immunohistochemical staining. Key results: KY19382 activated Wnt/β-catenin signaling and elevated the expression of ALP and proliferation marker PCNA in DP cells. KY19382 also increased hair length in ex vivo cultured mouse vibrissa follicles and induced hair regrowth in mice. Moreover, KY19382 significantly promoted the generation of de novo hair follicles as shown by WIHN and hair patch assays. Conclusion and Implications: These results indicate that KY19382 is a potential therapeutic drug that exhibits effective hair regeneration ability via activation of the Wnt/β-catenin signaling for alopecia treatments.

Peer review status:Published

12 Jun 2020Submitted to British Journal of Pharmacology
13 Jun 2020Submission Checks Completed
13 Jun 2020Assigned to Editor
17 Jun 2020Reviewer(s) Assigned
18 Aug 2020Review(s) Completed, Editorial Evaluation Pending
25 Aug 2020Editorial Decision: Revise Minor
06 Oct 20201st Revision Received
07 Oct 2020Submission Checks Completed
07 Oct 2020Assigned to Editor
10 Oct 2020Reviewer(s) Assigned
16 Nov 2020Review(s) Completed, Editorial Evaluation Pending
17 Nov 2020Editorial Decision: Revise Minor
03 Feb 20212nd Revision Received
03 Feb 2021Submission Checks Completed
03 Feb 2021Assigned to Editor
08 Feb 2021Reviewer(s) Assigned
17 Feb 2021Review(s) Completed, Editorial Evaluation Pending
20 Feb 2021Editorial Decision: Revise Minor
25 Feb 20213rd Revision Received
26 Feb 2021Submission Checks Completed
26 Feb 2021Assigned to Editor
28 Feb 2021Review(s) Completed, Editorial Evaluation Pending
28 Feb 2021Editorial Decision: Accept
10 Mar 2021Published in British Journal of Pharmacology. 10.1111/bph.15438