Altered Relaxin Protein Expression is Associated with Airway Remodeling Changes in Asthma
Presentation Number: SAT-396
Date of Presentation: June 15th, 2013
Simon G Royce*1, Chrishan S Samuel1 and Mimi LK Tang2
1Monash University, Melbourne, Australia, 2Murdoch Children's Research Institute, Melbourne, Australia
Background: Fibrotic airway remodeling is a therapeutic target in asthma that is not addressed by corticosteroid and β-agonist treatments. Recent transgenic mouse and genome wide studies have identified an important role for relaxin as an anti-fibrotic hormone in multiple organs beyond the reproductive tract, including the lung, where it is essential for regulating normal airway wall structure and function. However, little is known of the tissue distribution and cellular sources of relaxin and its cognate receptor, RXFP1, in the normal airway or in asthma.
Methods: We investigated the localization of relaxin and RXFP1 in 96 formalin-fixed paraffin-embedded endobronchial biopsies from patients with mild, moderate and severe asthma and in normal controls. Relaxin was detected immununohistochemically with a monoclonal antibody against human gene-2 (H2), and RXFP1 with the L7-2 polyclonal antibody. Epithelial, fibrotic and smooth muscle remodeling changes were measured morphometrically and compared to staining intensity and clinico-pathological data.
Results: Relaxin and RXFP1 staining was observed in a variety of cell types involved in airway remodeling including epithelial cells, fibroblasts and myocytes with the strongest staining observed in epithelial cells. This co-localization was suggestive of an autocrine/paracrine mode of hormone action. In biopsies from asthma patients, relaxin and RXFP1 staining was markedly reduced (both p<0.05); reticular basement membrane (collagen) thickness was increased (p<0.01); and epithelial cell thickness was increased (p<0.05) in all asthma groups versus controls.
Conclusions: These findings demonstrate for the first time that relaxin and its receptor are expressed within the human airway wall and localized specifically to airway structural cells; and confirm that the lung is both a source and target organ for relaxin. The hormone may play an important protective role in the lung as both relaxin and RXFP1 are reduced in asthma and are associated with airway remodeling changes including reticular basement membrane fibrosis and epithelial cell thickening.
Nothing to Disclose: SGR, CSS, MLT