Pyruvate Kinase M2 Promotes Hair Regeneration by Connecting Metabolic and Wnt/β-Catenin Signaling

Yeong Chan Ryu; You Rin Kim; Jiyeon Park; Sehee Choi; Won Ji Ryu; Geon Uk Kim; Eunhwan Kim; Yumi Hwang; Heejene Kim; Gyoonhee Han; Soung Hoon Lee; Kang Yell Choi

doi:10.3390/pharmaceutics14122774

Pyruvate Kinase M2 Promotes Hair Regeneration by Connecting Metabolic and Wnt/β-Catenin Signaling

Yeong Chan Ryu, You Rin Kim, Jiyeon Park, Sehee Choi, Won Ji Ryu, Geon Uk Kim, Eunhwan Kim, Yumi Hwang, Heejene Kim, Gyoonhee Han, Soung Hoon Lee, Kang Yell Choi

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Hair follicle stem cells (HFSCs) utilize glycolytic metabolism during their activation and anagen induction. However, the role of pyruvate kinase M2 (PKM2), which catalyzes the final step of glycolysis, in hair regeneration has not been elucidated. In this study, we investigated the expression pattern and activity of PKM2 during the depilation-induced anagen progression in mice. We found that TEPP-46, a selective activator of PKM2, enhanced hair re-growth and proliferation of HFSCs. PKM2 expression was increased via up-regulation of Wnt/β-catenin signaling, which is involved in hair regeneration. Moreover, a combined treatment with KY19382, a small molecule that activates Wnt/β-catenin signaling, and TEPP-46 significantly enhanced hair re-growth and wound-induced hair follicle neogenesis (WIHN). These results indicate that simultaneous activation of the PKM2 and Wnt/β-catenin signaling could be a potential strategy for treating alopecia patients.

Original language	English
Article number	2774
Journal	Pharmaceutics
Volume	14
Issue number	12
DOIs	https://doi.org/10.3390/pharmaceutics14122774
Publication status	Published - 2022 Dec

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) and a grant funded by the Korean government (MSIP) (2019R1A2C3002751, 2020M3E5E2040018). Y.C. RYU was supported by the Brain Korea 21 (BK21) Plus studentship from the NRF.

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© 2022 by the authors.

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Pharmaceutical Science

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title = "Pyruvate Kinase M2 Promotes Hair Regeneration by Connecting Metabolic and Wnt/β-Catenin Signaling",

abstract = "Hair follicle stem cells (HFSCs) utilize glycolytic metabolism during their activation and anagen induction. However, the role of pyruvate kinase M2 (PKM2), which catalyzes the final step of glycolysis, in hair regeneration has not been elucidated. In this study, we investigated the expression pattern and activity of PKM2 during the depilation-induced anagen progression in mice. We found that TEPP-46, a selective activator of PKM2, enhanced hair re-growth and proliferation of HFSCs. PKM2 expression was increased via up-regulation of Wnt/β-catenin signaling, which is involved in hair regeneration. Moreover, a combined treatment with KY19382, a small molecule that activates Wnt/β-catenin signaling, and TEPP-46 significantly enhanced hair re-growth and wound-induced hair follicle neogenesis (WIHN). These results indicate that simultaneous activation of the PKM2 and Wnt/β-catenin signaling could be a potential strategy for treating alopecia patients.",

author = "Ryu, {Yeong Chan} and Kim, {You Rin} and Jiyeon Park and Sehee Choi and Ryu, {Won Ji} and Kim, {Geon Uk} and Eunhwan Kim and Yumi Hwang and Heejene Kim and Gyoonhee Han and Lee, {Soung Hoon} and Choi, {Kang Yell}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) and a grant funded by the Korean government (MSIP) (2019R1A2C3002751, 2020M3E5E2040018). Y.C. RYU was supported by the Brain Korea 21 (BK21) Plus studentship from the NRF. Publisher Copyright: {\textcopyright} 2022 by the authors.",

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doi = "10.3390/pharmaceutics14122774",

language = "English",

volume = "14",

journal = "Pharmaceutics",

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T1 - Pyruvate Kinase M2 Promotes Hair Regeneration by Connecting Metabolic and Wnt/β-Catenin Signaling

AU - Ryu, Yeong Chan

AU - Kim, You Rin

AU - Park, Jiyeon

AU - Choi, Sehee

AU - Ryu, Won Ji

AU - Kim, Geon Uk

AU - Kim, Eunhwan

AU - Hwang, Yumi

AU - Kim, Heejene

AU - Han, Gyoonhee

AU - Lee, Soung Hoon

AU - Choi, Kang Yell

N1 - Funding Information: This work was supported by the National Research Foundation of Korea (NRF) and a grant funded by the Korean government (MSIP) (2019R1A2C3002751, 2020M3E5E2040018). Y.C. RYU was supported by the Brain Korea 21 (BK21) Plus studentship from the NRF. Publisher Copyright: © 2022 by the authors.

PY - 2022/12

Y1 - 2022/12

N2 - Hair follicle stem cells (HFSCs) utilize glycolytic metabolism during their activation and anagen induction. However, the role of pyruvate kinase M2 (PKM2), which catalyzes the final step of glycolysis, in hair regeneration has not been elucidated. In this study, we investigated the expression pattern and activity of PKM2 during the depilation-induced anagen progression in mice. We found that TEPP-46, a selective activator of PKM2, enhanced hair re-growth and proliferation of HFSCs. PKM2 expression was increased via up-regulation of Wnt/β-catenin signaling, which is involved in hair regeneration. Moreover, a combined treatment with KY19382, a small molecule that activates Wnt/β-catenin signaling, and TEPP-46 significantly enhanced hair re-growth and wound-induced hair follicle neogenesis (WIHN). These results indicate that simultaneous activation of the PKM2 and Wnt/β-catenin signaling could be a potential strategy for treating alopecia patients.

AB - Hair follicle stem cells (HFSCs) utilize glycolytic metabolism during their activation and anagen induction. However, the role of pyruvate kinase M2 (PKM2), which catalyzes the final step of glycolysis, in hair regeneration has not been elucidated. In this study, we investigated the expression pattern and activity of PKM2 during the depilation-induced anagen progression in mice. We found that TEPP-46, a selective activator of PKM2, enhanced hair re-growth and proliferation of HFSCs. PKM2 expression was increased via up-regulation of Wnt/β-catenin signaling, which is involved in hair regeneration. Moreover, a combined treatment with KY19382, a small molecule that activates Wnt/β-catenin signaling, and TEPP-46 significantly enhanced hair re-growth and wound-induced hair follicle neogenesis (WIHN). These results indicate that simultaneous activation of the PKM2 and Wnt/β-catenin signaling could be a potential strategy for treating alopecia patients.

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Pyruvate Kinase M2 Promotes Hair Regeneration by Connecting Metabolic and Wnt/β-Catenin Signaling

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