Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2021.064
Hair Growth Promotion by δ-Opioid Receptor Activation
Mei Zheng1, Nahyun Choi1, Gianfranco Balboni2, Ying Xia3 and Jong-Hyuk Sung1,4,*
1STEMORE Co. Ltd., Incheon 21983, Republic of Korea
2Department of Life and Environment Sciences, University of Cagliari, Cagliari 09124, Italy
3Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200032, China
4College of Pharmacy, Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea
*E-mail: brian99@yonsei.ac.kr
Tel: +82-32-749-4506, Fax: +82-32-209-8239
Received: April 1, 2021; Revised: May 24, 2021; Accepted: May 26, 2021; Published online: June 21, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Literature has revealed that the delta opioid receptor (DOR) exhibited diverse pharmacological effects on neuron and skin. In the present study, we have investigated whether the activation of DOR has hair-growth promotion effects. Compared with other opioid receptor, DOR was highly expressed in epidermal component of hair follicle in human and rodents. The expression of DOR was high in the anagen phase, but it was low in the catagen and telogen phases during mouse hair cycle. Topical application of UFP-512, a specific DOR agonist, significantly accelerated the induction of the anagen in C3H mice. Topical application of UFP-512 also increased the hair length in hair organ cultures and promoted the proliferation and the migration of outer root sheath (ORS) cells. Similarly, pharmacological inhibition of DOR by naltrindole significantly inhibited the anagen transition process and decreased hair length in hair organ cultures. Thus, we further examined whether Wnt/β-catenin pathway was related to the effects of DOR on hair growth. We found that Wnt/β-catenin pathway was activated by UFP-512 and siRNA for β-catenin attenuated the UFP-512 induced proliferation and migration of ORS cells. Collectively, result established that DOR was involved in hair cycle regulation, and that DOR agonists such as UFP-512 should be developed for novel hair-loss treatment.
Keywords: δ-opioid receptor, UFP-512, Outer root sheath cells, Hair growth, Anagen, Wnt/β-catenin


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