Chronic Exposure to TDI Induces Cell Migration and Invasion via TGF-β1 Signal Transduction

Dong Hee Han, Min Kyoung Shin, Jin Wook Oh, Junha Lee, Jung Suk Sung, Min Kim

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Toluene diisocyanate (TDI) is commonly used in manufacturing, and it is highly reactive and causes respiratory damage. This study aims to identify the mechanism of tumorigenesis in bronchial epithelial cells induced by chronic TDI exposure. In addition, transcriptome analysis results confirmed that TDI increases transforming growth factor-beta 1 (TGF-β1) expression and regulates genes associated with cancerous characteristics in bronchial cells. Our chronically TDI-exposed model exhibited elongated spindle-like morphology, a mesenchymal characteristic. Epithelial-mesenchymal transition (EMT) was evaluated following chronic TDI exposure, and EMT biomarkers increased concentration-dependently. Furthermore, our results indicated diminished cell adhesion molecules and intensified cell migration and invasion. In order to investigate the cellular regulatory mechanisms resulting from chronic TDI exposure, we focused on TGF-β1, a key factor regulated by TDI exposure. As predicted, TGF-β1 was significantly up-regulated and secreted in chronically TDI-exposed cells. In addition, SMAD2/3 was also activated considerably as it is the direct target of TGF-β1 and TGF-β1 receptors. Inhibiting TGF-β1 signaling through blocking of the TGF-β receptor attenuated EMT and cell migration in chronically TDI-exposed cells. Our results corroborate that chronic TDI exposure upregulates TGF-β1 secretion, activates TGF-β1 signal transduction, and leads to EMT and other cancer properties.

Original languageEnglish
Article number6157
JournalInternational Journal of Molecular Sciences
Volume24
Issue number7
DOIs
StatePublished - Apr 2023

Keywords

  • chronic exposure
  • epithelial-mesenchymal transition
  • invasion
  • migration
  • toluene diisocyanate
  • transforming growth factor-beta1

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