Kaempferol-Enhanced Migration and Differentiation of C2C12 Myoblasts via ITG1B/FAK/Paxillin and IGF1R/AKT/mTOR Signaling Pathways

Mol Nutr Food Res. 2024 Jul;68(14):e2300685. doi: 10.1002/mnfr.202300685. Epub 2024 Jun 11.

Abstract

Scope: Kaempferol (KMP), a bioactive flavonoid compound found in fruits and vegetables, contributes to human health in many ways but little is known about its relationship with muscle mass. The effect of KMP on C2C12 myoblast differentiation and the mechanisms that might underlie that effect are studied.

Methods and results: This study finds that KMP (1, 10 µM) increases the migration and differentiation of C2C12 myoblasts in vitro. Studying the possible mechanism underlying its effect on migration, the study finds that KMP activates Integrin Subunit Beta 1 (ITGB1) in C2C12 myoblasts, increasing p-FAK (Tyr398) and its downstream cell division cycle 42 (CDC42), a protein previously associated with cell migration. Regarding differentiation, KMP upregulates the expression of myosin heavy chain (MHC) and activates IGF1/AKT/mTOR/P70S6K. Interestingly, pretreatment with an AKT inhibitor (LY294002) and siRNA knockdown of IGF1R leads to a decrease in cell differentiation, suggesting that IGF1/AKT activation is required for KMP to induce C2C12 myoblast differentiation.

Conclusion: Together, the findings suggest that KMP enhances the migration and differentiation of C2C12 myoblasts through the ITG1B/FAK/paxillin and IGF1R/AKT/mTOR pathways. Thus, KMP supplementation might potentially be used to prevent or delay age-related loss of muscle mass and help maintain muscle health.

Keywords: C2C12 myoblast; differentiation; kaempferol; migration; muscle.

MeSH terms

  • Animals
  • Cell Differentiation* / drug effects
  • Cell Line
  • Cell Movement* / drug effects
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism
  • Integrin beta1* / metabolism
  • Kaempferols* / pharmacology
  • Mice
  • Myoblasts* / drug effects
  • Myoblasts* / metabolism
  • Paxillin* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Receptor, IGF Type 1* / genetics
  • Receptor, IGF Type 1* / metabolism
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • Kaempferols
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • mTOR protein, mouse
  • kaempferol
  • Integrin beta1
  • Paxillin
  • Receptor, IGF Type 1
  • Ptk2 protein, mouse
  • Itgb1 protein, mouse
  • Focal Adhesion Kinase 1
  • Pxn protein, mouse