Abstract
Introduction and aim. It has been recently discovered that Rora expression is increased in the lungs of COPD patients and offers a new perspective in the pathogenesis of emphysema, related with DNA damage response network. As smoking is also a possible pathogenetic factor in Fibrotic Interstitial Pneumonias we hypothesized that Rora expression is altered in lung tissue of these patients. Methodology. Immunohistochemical staining of type II Pneumocytes in between the fibroblastic foci (FF), as well as, in and around the fibroblastic area, fibroblasts (in the interstitial spaces and within the FF), was evaluated for nuclear and cytoplasmic Rora expression. IPF (n=9), non-IPF (COP n=11, fNSIP n=2) and RA-ILD (n=2) speciments were analysed.
Results. Type II Pneumocytes: A similar Rora nuclear expression in non fibrotic areas was observed between controls, IPF and COP. However, a significant decrease in Rora nuclear levels was measured in areas surrounding and in the FF in IPF and COP patients when compared with pneumocytes in between the fibrotic lesions. Inversely, the cytoplasmic localization of Rora was more pronounced in FF associated areas as compared to tissue distant from the FF. Fibroblasts: Rora expression was undetectable in fibroblasts in the interstitial spaces. In contrast, fibroblasts within the FF exhibit both nuclear and cytoplasmic localization of Rora. Importantly, in IPF a trend of higher nuclear expression was observed when compared to COP. Finally, smoking appears to downregulate Rora nuclear levels in IPF.
Conclusion: Our study offers novel insights regarding the cell-type dependent expression of Rora in fibrotic lung tissue.
- © 2014 ERS