Saturday, 17 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)
Pulmonary fibrosis occurs in a wide variety of illnesses, including systemic disorders as well as primary lung diseases. Fibrotic changes can also appear as sequelae to insults by a diverse group of infectious, environmental, and therapeutic exposures. It is one of the devastating diseases, however, there are very few therapeutic options. Therefore, the understanding the pathogenic mechanisms implicated in the process of fibrosis is important. Recently, one potential emerging mechanism for pulmonary fibrotic changes involves the endoplasmic reticulum (ER), the organelle responsible for protein folding, maturation, quality control, and trafficking. However, to date, there is little information on which molecular mechanisms related to ER stress induces fibrotic changes in the lung. In this study, we used a murine model of bleomycin-inducd lung fibrosis to evaluate the therapeutic potential of ER stress inhibitor on pulmonary fibrosis and to investigate the molecular action mechanisms. These results showed that the increased the expression of ER stress markers and the protein levels of unfolded-protein response (UPR)-related markers in lung tissues, increased numbers of airway inflammatory cells, airway hyperresponsiveness, and increased levels of pro-inflammatory cytokines, TGF-β1, and increased nuclear translocation of NF-κB. In addition, the bloemycin-inhaled mice developed features of pulmonary fibrotic changes, including thickening of the peribronchial smooth muscle layer, subepithelial collagen deposition, increased airway mucus production, and depositon of decorin. Administration of 4-PBA reduced the pathophysiological symptoms of pulmonary fibrosis, increased NF-κB activation, pro-inflammatory cytokines, and TGF-β1 in lungs as well as the increased expression of ER stress markers and the protein levels of UPR-related markers after bleomycin inhalation. These results indicate that inhibition of ER stress may attenuate pulmonary fibrotic changes through the regulation of deconrin and inhibit NF-κB pathway leading to increase pro-fibrotic cytokines.