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

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

doi:10.3390/pharmaceutics14122774

Cited by 3 publications

(3 citation statements)

References 46 publications

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“…PKM2 is a key enzyme in the glycolysis pathway that produces the necessary bioenergetics for the repeated cycles of self-renewal and differentiation required by stem cells. PKM2 was elevated during the transition to the anagen phase in hair follicles, and levels remained elevated in this phase, while lower levels were found in the androgenic mouse model [ 71 ]. A reduced level of PKM2 was observed in testosterone-treated mice, while elevated expression of this protein occurred in the androgenic mice, regrowing hair after treatment with minoxidil (1%, w / w ), AA in ethanol (1%), and AA–TF#15 (1%).…”

Section: Discussionmentioning

confidence: 99%

Topical Delivery of Atraric Acid Derived from Stereocaulon japonicum with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia

et al. 2023

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Atraric acid (AA) is a phenolic compound isolated from Stereocaulon japonicum that has demonstrated anti-androgen properties and was used to design an alternative formulation for the treatment of alopecia. This new topical formulation was designed using a solvent mixture system composed of ethanol as a volatile vehicle, oleic acid as a permeation enhancer, and water for skin hydration. The ideal topical AA formulation (AA–TF#15) exhibited an 8.77-fold higher human skin flux and a 570% increase in dermal drug deposition, compared to 1% (w/w) AA in ethanol. In addition, compared to other formulations, AA–TF#15 (1% [w/w] AA) activated keratinocytes and human dermal papilla cell proliferation at a concentration of 50 µM AA, which is equivalent to 50 µM minoxidil. Moreover, AA–TF#15 treatment produced a significant increase in hair regrowth by 58.0% and 41.9% compared to the 1% (w/w) minoxidil and oral finasteride (1 mg/kg)-treated mice. In addition, AA–TF#15 showed a higher expression level of aldehyde dehydrogenase 1, β-catenin, cyclin D1, and pyruvate kinase M2 proteins in the skin of AA–TF#15-treated mice compared to that of those treated with minoxidil and oral finasteride. These findings suggest AA–TF#15 is an effective formulation for the treatment of scalp androgenic alopecia.

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Section: Discussionmentioning

confidence: 99%

Topical Delivery of Atraric Acid Derived from Stereocaulon japonicum with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia

et al. 2023

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“…The lysates were centrifuged at 15,000 rpm for 30 min. An equal amount of each protein was incubated with reaction buffer (100 mM KCl, 50 mM Tris, pH 7.5, 5 mM, 0.6 mM ADP, 0.5 mM phosphoenolpyruvate (PEP), 10 µM fructose-1,6-bisphosphate (FBP), 240 µM NADH, and 8 units of lactate dehydrogenase (LDH), as previously described [ 22 ]. The change in absorbance at 320 nm owing to the oxidation of NADH was measured using a FLUOstar OPTIMA luminometer (BMG Labtech, Offenburg, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…We confirmed that TEPP-46, a PKM2 activator, promoted the migration of human keratinocytes and wound healing in mice. Moreover, combination treatment with TEPP-46 and KY19382, a small molecule that activates Wnt/β-catenin signaling by interfering with cytosolic CXXC-type zinc finger protein 5 (CXXC5) function via CXXC5-Dishevelled interaction [ 22 ], significantly enhanced wound healing, followed by re-epithelialization and collagen deposition. PKM2 and its activity were highly increased in the wound sites by cotreatment.…”

Section: Introductionmentioning

confidence: 99%

Pyruvate Kinase M2 Accelerates Cutaneous Wound Healing via Glycolysis and Wnt/β-Catenin Signaling

et al. 2023

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Cutaneous wound healing is a complex and dynamic process with high energy demand. The activation of glycolysis is essential for restoring the structure and function of injured tissues in wounds. Pyruvate kinase M2 (PKM2) is an enzyme that plays a crucial role in the last step of glycolysis. PKM2-mediated glycolysis is known to play an important role in diseases related to regeneration and inflammation. However, the role of PKM2 in wound healing has not been fully elucidated. In this study, we found that PKM2 expression and pyruvate kinase (PK) activity were increased with the activation of Wnt/β-catenin signaling during wound healing in mice. TEPP-46, an allosteric activator of PKM2, enhanced HaCaT human keratinocyte migration and cutaneous wound healing with an increment of PK activity. Moreover, we confirmed the effect of co-treatment with TEPP-46 and KY19382, a Wnt/β-catenin signaling activator through the interference with the CXXC-type zinc finger protein 5 (CXXC5) Dishevelled interaction, on wound healing. The combination treatment significantly accelerated wound healing, which was confirmed by the expression level of PCNA, keratin 14, and α-SMA. Furthermore, co-treatment induced angiogenesis in the wound beds. Overall, activation of both glycolysis and Wnt/β-catenin signaling has the potential to be used as a therapeutic approach for wound healing.

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The Role of Mesenchymal Stem Cells in Hair Regeneration and Hair Cycle

Ma,

Cheng,

et al. 2024

Stem Cells and Development

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

Cited by 3 publications

References 46 publications

Topical Delivery of Atraric Acid Derived from Stereocaulon japonicum with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia

Topical Delivery of Atraric Acid Derived from Stereocaulon japonicum with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia

Pyruvate Kinase M2 Accelerates Cutaneous Wound Healing via Glycolysis and Wnt/β-Catenin Signaling

The Role of Mesenchymal Stem Cells in Hair Regeneration and Hair Cycle

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