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Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells

Biomolecules & Therapeutics 2021년 29권 2호 p.211 ~ 219
최연경, 강정일, 현진원, 고영상, 강지훈, 현창구, 윤경섭, 이광식, 이춘몽, 김태양, 유은숙, 강희경,
소속 상세정보
최연경 ( Choi Youn-Kyung ) - Jeju National University School of Medicine Department of Medicine
강정일 ( Kang Jung-Il ) - Jeju National University School of Medicine Department of Medicine
현진원 ( Hyun Jin-Won ) - Jeju National University School of Medicine Department of Medicine
고영상 ( Koh Young-Sang ) - Jeju National University School of Medicine Department of Medicine
강지훈 ( Kang Ji-Hoon ) - Jeju National University School of Medicine Department of Medicine
현창구 ( Hyun Chang-Gu ) - Jeju National University Department of Chemistry and Cosmetics
윤경섭 ( Yoon Kyung-Sup ) - Jeju National University Department of Chemistry and Cosmetics
이광식 ( Lee Kwang-Sik ) - Coreana Cosmetic Co. Ltd.
이춘몽 ( Lee Chun-Mong ) - Coreana Cosmetic Co. Ltd.
김태양 ( Kim Tae-Yang ) - Coreana Cosmetic Co. Ltd.
유은숙 ( Yoo Eun-Sook ) - Jeju National University School of Medicine Department of Medicine
강희경 ( Kang Hee-Kyoung ) - Jeju National University School of Medicine Department of Medicine

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.

키워드

Myristoleic acid; Dermal papilla cells; Anagen; Autophagy; Wnt/β-catenin; ERK

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