Rhoa-dependent HGF and c-MET mediate gas6-induced inhibition of epithelial–mesenchymal transition, migration, and invasion of lung alveolar epithelial cells

Jihye Jung, Kyungwon Yang, Hee Ja Kim, Ye Ji Lee, Minsuk Kim, Youn Hee Choi, Jihee Lee Kang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Previously, we demonstrated that growth arrest-specific protein 6 (Gas6)/Axl or Mer signaling inhibited the transforming growth factor (TGF)-β1-induced epithelial–mesenchymal transition (EMT) in lung epithelial cells. Hepatocyte growth factor (HGF) has also been shown to inhibit TGF-β1-induced changes in EMT markers. Here, we examined whether Gas6 signaling can induce the production of HGF and c-Met in lung alveolar epithelial cells to mediate the inhibition of EMT and to inhibit the migration and invasion of epithelial cells. The inhibition of the RhoA/Rho kinase pathway, using either a RhoA-targeted small interfering RNA (siRNA) or the Rho kinase pharmacologic inhibitor Y27362, prevented the inhibition of TGF-β1-induced EMT in LA-4 cells and primary alveolar type II (AT II) epithelial cells. The c-Met antagonist PHA-665752 also blocked the anti-EMT effects associated with Gas6. Moreover, treatment with Y27362 or PHA-665752 prevented the Gas6-mediated inhibition of TGF-β1-induced migration and invasion. Our data provided evidence that the RhoA-dependent production of HGF and c-Met mediated the Gas6-induced inhibition of EMT, migration and invasion in lung alveolar epithelial cells. Thus, Gas6/Axl and Mer/RhoA signaling may be necessary for the maintenance of homeostasis in the alveolar epithelium, via HGF and c-Met.

Original languageEnglish
Article number565
JournalBiomolecules
Volume9
Issue number10
DOIs
StatePublished - Oct 2019

Keywords

  • C-Met
  • Epithelial-mesenchymal transition
  • Growth arrest-specific protein 6
  • Hepatocyte growth factor
  • Lung epithelial cells

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