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RhoA-Dependent HGF and c-Met Mediate Gas6-Induced Inhibition of Epithelial-Mesenchymal Transition, Migration, and Invasion of Lung Alveolar Epithelial Cells
- Title
- RhoA-Dependent HGF and c-Met Mediate Gas6-Induced Inhibition of Epithelial-Mesenchymal Transition, Migration, and Invasion of Lung Alveolar Epithelial Cells
- Authors
- Jung, Jihye; Yang, Kyungwon; Kim, Hee-Ja; Lee, Ye-Ji; Kim, Minsuk; Choi, Youn-Hee; Kang, And Jihee Lee
- Ewha Authors
- 이지희; 최윤희; 김민석
- SCOPUS Author ID
- 이지희; 최윤희; 김민석
- Issue Date
- 2019
- Journal Title
- BIOMOLECULES
- ISSN
- 2218-273X
- Citation
- BIOMOLECULES vol. 9, no. 10
- Keywords
- growth arrest-specific protein 6; hepatocyte growth factor; c-Met; epithelial-mesenchymal transition; lung epithelial cells
- Publisher
- MDPI
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Previously, we demonstrated that growth arrest-specific protein 6 (Gas6)/Axl or Mer signaling inhibited the transforming growth factor (TGF)-beta 1-induced epithelial-mesenchymal transition (EMT) in lung epithelial cells. Hepatocyte growth factor (HGF) has also been shown to inhibit TGF-beta 1-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-beta 1-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-beta 1-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.
- DOI
- 10.3390/biom9100565
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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