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Macrophages programmed by apoptotic cells inhibit epithelial-mesenchymal transition in lung alveolar epithelial cells via PGE(2), PGD(2), and HGF
- Title
- Macrophages programmed by apoptotic cells inhibit epithelial-mesenchymal transition in lung alveolar epithelial cells via PGE(2), PGD(2), and HGF
- Authors
- Yoon, Young-So; Lee, Ye-Ji; Choi, Youn-Hee; Park, Young Mi; Kang, Jihee Lee
- Ewha Authors
- 이지희; 최윤희; 박영미
- SCOPUS Author ID
- 이지희; 최윤희; 박영미
- Issue Date
- 2016
- Journal Title
- SCIENTIFIC REPORTS
- ISSN
- 2045-2322
- Citation
- SCIENTIFIC REPORTS vol. 6
- Publisher
- NATURE PUBLISHING GROUP
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Apoptotic cell clearance results in the release of growth factors and the action of signaling molecules involved in tissue homeostasis maintenance. Here, we investigated whether and how macrophages programmed by apoptotic cells inhibit the TGF-beta 1-induced Epithelial-mesenchymal transition (EMT) process in lung alveolar epithelial cells. Treatment with conditioned medium derived from macrophages exposed to apoptotic cells, but not viable or necrotic cells, inhibited TGF-beta 1-induced EMT, including loss of E-cadherin, synthesis of N-cadherin and alpha-smooth muscle actin, and induction of EMT-activating transcription factors, such as Snail1/2, Zeb1/2, and Twist1. Exposure of macrophages to cyclooxygenase (COX-2) inhibitors (NS-398 and COX-2 siRNA) or RhoA/Rho kinase inhibitors (Y-27632 and RhoA siRNA) and LA-4 cells to antagonists of prostaglandin E-2 (PGE(2)) receptor (EP4 [AH-23848]), PGD(2) receptors (DP1 [BW-A868C] and DP2 [BAY-u3405]), or the hepatocyte growth factor (HGF) receptor c-Met (PHA-665752), reversed EMT inhibition by the conditioned medium. Additionally, we found that apoptotic cell instillation inhibited bleomycin-mediated EMT in primary mouse alveolar type II epithelial cells in vivo. Our data suggest a new model for epithelial cell homeostasis, by which the anti-EMT programming of macrophages by apoptotic cells may control the progressive fibrotic reaction via the production of potent paracrine EMT inhibitors.
- DOI
- 10.1038/srep20992
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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