Biomolecules & Therapeutics 2021; 29(2): 211-219  https://doi.org/10.4062/biomolther.2020.169
Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells
Youn Kyung Choi1,2, Jung-Il Kang1,2, Jin Won Hyun1,2, Young Sang Koh1,2, Ji-Hoon Kang1, Chang-Gu Hyun2,3, Kyung-Sup Yoon3, Kwang Sik Lee4, Chun Mong Lee4, Tae Yang Kim4, Eun-Sook Yoo1,2 and Hee-Kyoung Kang1,2,*
1Department of Medicine, School of Medicine, Jeju National University, Jeju 63243,
2Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243,
3Department of Chemistry & Cosmetics, Jeju National University, Jeju 63243,
4DSongpa R&D Center, Coreana Cosmetic Co., Ltd, Cheonan 31041, Republic of Korea
*E-mail: pharmkhk@jejunu.ac.kr
Tel: +82-64-754-3846, Fax: +82-64-702-2687
Received: September 28, 2020; Revised: December 11, 2020; Accepted: January 6, 2021; Published online: February 1, 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
Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β (Ser9) and β-catenin (Ser552 and Ser675). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202/Tyr204)-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.
Keywords: Myristoleic acid, Dermal papilla cells, Anagen, Autophagy, Wnt/β-catenin, ERK

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