Activation of protease-activated receptor 2 elicits epithelial-mesenchymal transition in HBE cells via ROS signaling

As a critical event involved in the airway remodeling, epithelial-mesenchymal transition (EMT) of bronchial epithelial cells occurs in a range of respiratory disorders such as asthma and pulmonary fibrosis. Since protease-activated receptor 2 (PAR2) is well documented to be implicated in airway disorders, little is known about its role in EMT so far. Our study was to determine the impact of PAR2 activation on EMT and the underlying mechanisms. We used human bronchial epithelial (HBE) cells to be challenged by tryptase (a nature agonist of PAR2) and the synthetic peptide of SLIGKV-NH2 (a specific agonist of PAR2). The results showed that both two agonists dramatically promoted cell migration with a loss of E-cadherin as well as increases of N-cadherin and α-smooth muscle actin (α-SMA) in HBE. These potentiated effects were all abolished by the specific PAR2 antagonist FSLLRY-NH2 (FS). It was also revealed that either tryptase or SLIGKV-NH2 could elevate the intracellular level of reactive oxygen species (ROS), which were completely reversed by FS, implying an involved pathway of ROS. Coincidently, by using N-acety-1-cysteine (NAC), PAR2-induced cell migration was significantly inhibited with down-regulated levels of N-cadherin and α-SMA. These findings are the first to demonstrate that PAR2 activation could trigger EMT process in HBE which probably due to the overproduction of ROS. The present study not only highlights a novel profile of PAR2 as a regulator o...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway Cell Biology and Immunopathology Source Type: research