Dataset Information

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.

SUBMITTER: Ryu YC

PROVIDER: S-EPMC9781674 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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

Ryu Yeong Chan YC Kim You-Rin YR Park Jiyeon J Choi Sehee S Ryu Won-Ji WJ Kim Geon-Uk GU Kim Eunhwan E Hwang Yumi Y Kim Heejene H Han Gyoonhee G Lee Soung-Hoon SH Choi Kang-Yell KY

Pharmaceutics 20221213 12

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 express ...[more]

PMID: 36559274

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Project description:Regeneration of periodontal tissue, particularly the cementum-periodontal ligament (PDL)-bone complex, has long been challenging because the differentiation kinetics of cells and the molecular pathways contributing to the regeneration process are largely unknown. We aimed to evaluate the cell behavior and molecular pathways that contribute to periodontal tissue regeneration in vivo. We analyzed the process of periodontal tissue regeneration through subrenal capsule transplantation of immediately extracted molars in mice. We showed that the regenerated periodontal tissue in the subrenal capsule was morphologically comparable to the intact periodontal tissue, with increased cellular cementum thickness in the apical region. Cell tracing analysis revealed that the cells comprising the regenerated periodontal tissue were derived from transplanted teeth and were indispensable for periodontal tissue regeneration, whereas recipient mouse-derived cells partly contributed to angiogenesis. Bioinformatics analysis based on the gene expression profile in the transplanted teeth indicated that Wnt/β-catenin signaling is involved in periodontal tissue regeneration, which was further confirmed through β-catenin immunohistochemistry. Moreover, the constitutive activation of β-catenin in the cells of transplanted teeth was found to promote accelerated cellular cementum apposition, while the conditional knockout of β-catenin in the cells of transplanted teeth suppressed cellular cementum apposition. Notably, the manipulation of Wnt/β-catenin signaling did not interfere with the bone-PDL-cementum complex, while endogenous osteoclast activity was affected in bone. Our results demonstrated the essential roles of endogenous PDL cells in periodontal tissue regeneration and that Wnt/β-catenin signaling is involved in this process, particularly cellular cementum apposition. Hence, controlling this pathway could promote cementum regeneration, which is a critical process for the regeneration of the cementum-PDL-bone complex. This study provides novel insights into cell behavior and signaling pathways that will advance practical periodontal tissue regeneration.

Dataset Information

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

Publications

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

Similar Datasets

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