Stress Inhibits Myogenic Differentiation via Transcriptome Remodeling and GR-Mediated Suppression of the

Jian Qin1,2, Hao Zhang1, Zhenyue Li1

  • 1College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Jinzhong, Shanxi 030801, China.

Insights

Stress, induced by dexamethasone, impairs sheep fetal myoblast differentiation by altering gene expression and suppressing the ITGA11 signaling pathway. This research clarifies stress impacts on muscle development and livestock quality.

Area of Science:

  • Muscle biology
  • Cellular stress response
  • Molecular signaling

Background:

  • Myogenic differentiation is crucial for muscle development.
  • The impact of stress on this process is not fully understood.
  • Integrin-mediated signaling plays a role in muscle formation.

Purpose of the Study:

  • Investigate how stress affects sheep fetal myoblast differentiation.
  • Elucidate the regulatory mechanisms involved, focusing on integrin signaling.
  • Identify key genes and pathways affected by stress.

Main Methods:

  • Sheep fetal myoblast (SFM) culture under normal and dexamethasone (Dex)-induced stress.
  • Transcriptomic analysis to identify differentially expressed genes (DEGs).
  • RU486 (glucocorticoid receptor antagonist) treatment and gene/protein expression analysis.
  • Overexpression and interference experiments for ITGA11.

Main Results:

  • Dexamethasone reversed the upregulation/downregulation of 153 DEGs during differentiation.
  • Affected pathways included ECM-receptor interaction, focal adhesion, and PI3K-Akt.
  • RU486 reversed Dex-induced changes in the FBLN5/Integrin-FAK/Paxillin-Akt-GSK3β cascade.
  • ITGA11 overexpression promoted differentiation and rescued Dex-induced suppression via FAK/Paxillin-Akt-GSK3β.

Conclusions:

  • Stress inhibits SFM differentiation through transcriptome remodeling.
  • Glucocorticoid receptor-mediated suppression of the ITGA11-FAK/Paxillin-Akt-GSK3β cascade is a key mechanism.
  • Findings offer insights into stress-induced muscular issues and livestock production.

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