Chemical Chaperone of Endoplasmic Reticulum Stress Inhibits Epithelial-Mesenchymal Transition Induced by TGF- β 1 in Airway Epithelium via the c-Src Pathway

• Published in: Mediators of inflammation Vol. 2017; pp. 8123281 - 9
• Main Authors: Lee, Heung-Man, Kang, Ju-Hyung, Shin, Jae-Min, Lee, Seoung-Ae, Park, Il-Ho
• Format: Journal Article
• Language: English
• Published: United States 2017
• Subjects: A549 Cells; Cell Movement - drug effects; Endoplasmic Reticulum Stress - drug effects; Epithelial-Mesenchymal Transition - drug effects; Genes, src - genetics; Genes, src - physiology; Humans; Nasal Polyps - metabolism; Organ Culture Techniques; Signal Transduction - drug effects; Transforming Growth Factor beta1 - pharmacology
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2017/8123281

Epithelial-mesenchymal transition (EMT) is a biological process that allows epithelial cells to assume a mesenchymal cell phenotype. EMT is considered as a therapeutic target for several persistent inflammatory airway diseases related to tissue remodeling. Herein, we investigated the role of endoplasmic reticulum (ER) stress and c-Src in TGF- 1-induced EMT. A549 cells, primary nasal epithelial cells (PNECs), and inferior nasal turbinate organ cultures were exposed to 4-phenylbutylic acid (4PBA) or PP2 and then stimulated with TGF- 1. We found that E-cadherin, vimentin, fibronectin, and -SMA expression was increased in nasal polyps compared to inferior turbinates. TGF- 1 increased the expression of EMT markers such as E-cadherin, fibronectin, vimentin, and -SMA and ER stress markers (XBP-1s and GRP78), an effect that was blocked by PBA or PP2 treatment. 4-PBA and PP2 also blocked the effect of TGF- 1 on migration of A549 cells and suppressed TGF- 1-induced expression of EMT markers in PNECs and organ cultures of inferior turbinate. In conclusion, we demonstrated that 4PBA inhibits TGF- 1-induced EMT via the c-Src pathway in A549 cells, PNECs, and inferior turbinate organ cultures. These results suggest an important role for ER stress and a diverse role for TGF- 1 in upper airway chronic inflammatory disease such as CRS.