2. Academic Validation
  3. Alpha-ketoglutarate restores oral epithelial homeostasis via FOXM1-mediated cell cycle regulation

Alpha-ketoglutarate restores oral epithelial homeostasis via FOXM1-mediated cell cycle regulation

  • Sci China Life Sci. 2025 Sep 1. doi: 10.1007/s11427-024-2984-1.
Yuan Wang # 1,  Yimeng Cai # 1,  Qi Yin 1,  Shuqin Cao 1,  Yuyu Li 1,  Yuhan Li 1,  Qiwen Li 1,  Qian Wang 1,  Pochun Lin 1,  Li Mei 2,  Malcolm Xing 3,  Leixiao Yu 4,  Zhipeng Fan 5 6 7,  Quan Yuan 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
  • 2 Department of Oral Sciences, Faculty of Dentistry, University of Otago, Dunedin, 9054, New Zealand.
  • 3 Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada.
  • 4 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China. leixiaoyu@scu.edu.cn.
  • 5 Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100050, China. zpfan@ccmu.edu.cn.
  • 6 Beijing Laboratory of Oral Health, Capital Medical University, Beijing, 100050, China. zpfan@ccmu.edu.cn.
  • 7 Research Unit of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, 100050, China. zpfan@ccmu.edu.cn.
  • 8 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China. yuanquan@scu.edu.cn.
  • # Contributed equally.
PMID: 40908367 DOI: 10.1007/s11427-024-2984-1
Abstract

The rapid repair of intraoral mucosal injuries is crucial for restoring oral epithelial homeostasis. Alpha-ketoglutarate (αKG), a multi-potential metabolite involved in protein synthesis, epigenetic regulation, and immune response, holds the potential in tissue homeostasis and wound repair. Here, we report that administration of αKG accelerates palatal wound healing, with enhanced re-epithelialization and increased Collagen deposition. αKG increases the number of Ki67+ cells in the palatal epithelium and elevates the percentage of EdU+ cells in cultured human gingival epithelial cells (HGEs). Importantly, αKG treatment upregulates cell cycle-related pathways, primarily modulating the activity of CDK1-cyclin A and CDK1-cyclin B complexes. Mechanistically, αKG promotes the expression of FOXM1 and mediates the downstream cell cycle regulation. To further optimize local delivery of αKG, we develop the polyethyleneimine (PEI)/polyacrylic acid (PAA)/αKG supramolecular network to promote oral wound healing. Taken together, our findings demonstrate that αKG restores oral epithelial homeostasis via FOXM1-mediated cell cycle regulation, highlighting its therapeutic potential for oral wound repair.

Keywords

FOXM1; alpha-ketoglutarate; cell cycle; oral epithelial homeostasis.

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