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The interaction of HT-2 toxin and Akt1 on gene expression regulation in Kashin-Beck disease pathogenesis

Xinhua Liao1, Xiaodong Yang2, Xiaoqian Jia3

  • 1General Surgery Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, PR China.

Toxicon : Official Journal of the International Society on Toxinology
|May 31, 2025
PubMed
Abstract

Insights

This study reveals how T-2 toxin metabolite HT-2 and Akt1 affect chondrocyte gene expression, offering insights into Kashin-Beck disease (KBD) pathogenesis. Akt1 influences autophagy, proliferation, and glycolysis under HT-2 exposure, contributing to KBD.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Kashin-Beck disease (KBD) is a severe endemic osteochondropathy.
  • The T-2 toxin metabolite HT-2 and the Akt1 signaling pathway are implicated in KBD pathogenesis.
  • Understanding their effects on chondrocyte gene expression is crucial.

Purpose of the Study:

  • To investigate the individual and combined effects of HT-2 and Akt1 on human chondrocyte gene expression.
  • To elucidate the roles of HT-2 and Akt1 in the molecular mechanisms underlying KBD.
  • To identify key genes and pathways involved in chondrocyte dysfunction.

Main Methods:

  • Human chondrocytes (C28/I2) were treated with HT-2 toxin and/or transfected with siAkt1.
  • Differential gene expression was analyzed using high-throughput RNA sequencing.
  • Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were performed.

Main Results:

  • HT-2 exposure significantly altered expression of genes involved in cell adhesion, PI3K-Akt signaling, and extracellular matrix interactions.
  • Silencing Akt1 affected metabolic pathways, including fructose/mannose metabolism and glycolysis.
  • Combined HT-2 and siAkt1 treatment downregulated adhesion and PI3K-Akt signaling pathways, with significant changes in specific genes like CCND2 and MMP9.

Conclusions:

  • Akt1 plays a significant role in modulating chondrocyte responses to HT-2 exposure.
  • Akt1 influences autophagy, cell proliferation, and glycolysis, contributing to KBD pathogenesis.
  • The findings provide molecular targets for KBD intervention.
Keywords:
Akt1Environment-gene interactionHT-2 toxinKashin-Beck disease (KBD)WGCNA

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