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Gas6 Prevents Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells via Production of PGE2, PGD2 and Their Receptors
- Source :
- Cells, Vol 8, Iss 7, p 643 (2019), Cells, Volume 8, Issue 7
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- The epithelial-mesenchymal transition (EMT) is important in organ fibrosis. We hypothesized that growth arrest-specific protein 6 (Gas6) and its underlying mechanisms play roles in the prevention of EMT in alveolar epithelial cells (ECs). In this study, to determine whether Gas6 prevents TGF-&beta<br />1-induced EMT in LA-4 and primary alveolar type II ECs, real-time PCR and immunoblotting in cell lysates and ELISA in culture supernatants were performed. Migration and invasion assays were performed using Transwell chambers. Pretreatment of ECs with Gas6 inhibited TGF-&beta<br />1-induced EMT based on cell morphology, changes in EMT marker expression, and induction of EMT-activating transcription factors. Gas6 enhanced the levels of cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) and PGD2 as well as of their receptors. COX-2 inhibitors and antagonists of PGE2 and PGD2 receptors reversed the inhibition of TGF-&beta<br />1-induced EMT, migration, and invasion by Gas6. Moreover, knockdown of Axl or Mer reversed the enhancement of PGE2 and PGD2 and suppression of EMT, migration and invasion by Gas6. Our data suggest Gas6-Axl or -Mer signalling events may reprogram ECs to resist EMT via the production of PGE2, PGD2, and their receptors.
- Subjects :
- Primary Cell Culture
Receptors, Prostaglandin
epithelial-mesenchymal transition
Cell morphology
alveolar epithelial cells
Article
Dinoprostone
Transforming Growth Factor beta1
prostaglandins
Mice
Cell Movement
Fibrosis
Proto-Oncogene Proteins
Gas6
medicine
Animals
Humans
Receptors, Prostaglandin E
Epithelial–mesenchymal transition
Receptors, Immunologic
Prostaglandin E2
Receptor
Transcription factor
lcsh:QH301-705.5
Gene knockdown
c-Mer Tyrosine Kinase
Prostaglandin D2
GAS6
Chemistry
Receptor Protein-Tyrosine Kinases
General Medicine
medicine.disease
Axl Receptor Tyrosine Kinase
Recombinant Proteins
Cell biology
HEK293 Cells
lcsh:Biology (General)
A549 Cells
Cyclooxygenase 2
Gene Knockdown Techniques
embryonic structures
Intercellular Signaling Peptides and Proteins
lipids (amino acids, peptides, and proteins)
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 8
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....686019aaff5a1b6c6909f474836ff5f2