MUC5B is expressed by bronchoalveolar epithelia and is associated with ER stress in idiopathic pulmonary fibrosis and rheumatoid arthritis associated interstitial lung disease

Abstract

Introduction: Given phenotypic similarities between rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF) and our recent findings demonstrating that the MUC5B rs35705950 minor allele is a risk factor for both IPF and RA-ILD, we hypothesized that IPF and RA-ILD lung tissue would demonstrate similar localization of MUC5B and that MUC5B expression would be associated with endoplasmic reticulum (ER) stress, a mechanism of cell injury and repair. Methods: We analyzed lung tissue from patients with IPF and RA-ILD for concordant expression of MUC5B nd other relevant markers of pulmonary fibrosis. Results: Similar to our findings in IPF, we found that MUC5B is expressed in lung tissue from patients with RA-ILD (Figures A, B) and MUC5B mRNA co-localizes with surfactant protein C (SPC) mRNA, a marker of type 2 alveolar epithelial cells (Figure C). Furthermore, using fluorescent mRNA in situ hybridization, we found that epithelial cells expressing MUC5B are also undergoing endoplasmic reticulum (ER) stress (Figure D). Conclusion: We conclude that MUC5B is expressed by the bronchoalveolar epithelia and MUC5B mRNA is co-expressed by cells expressing surfactant protein C in both IPF and RA-ILD. Importantly, cells that express MUC5B in both disease states are undergoing ER stress.