RhoA-Dependent HGF and c-Met Mediate Gas6-Induced Inhibition of Epithelial-Mesenchymal Transition, Migration, and Invasion of Lung Alveolar Epithelial Cells.
Biomolecules
; 9(10)2019 10 04.
Article
de En
| MEDLINE
| ID: mdl-31590238
ABSTRACT
Previously, we demonstrated that growth arrest-specific protein 6 (Gas6)/Axl or Mer signaling inhibited the transforming growth factor (TGF)-ß1-induced epithelial-mesenchymal transition (EMT) in lung epithelial cells. Hepatocyte growth factor (HGF) has also been shown to inhibit TGF-ß1-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-ß1-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-ß1-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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Facteur de croissance des hépatocytes
/
Protéines proto-oncogènes c-met
/
Protéine G RhoA
/
Protéines et peptides de signalisation intercellulaire
/
Pneumocytes
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
Biomolecules
Année:
2019
Type de document:
Article