Cartilage Oligomeric Matrix Protein in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) progressive and life threatening disease with median survival of 2.5-3 years characterized by abnormal lung remodeling, epithelial cell hyperplasia, myofibroblast foci formation extracellular matrix deposition. Analysis of gene expression. microarray data revealed that cartilage oligomeric matric protein (COMP), a non-collagenous extracellular matrix protein is among the most significantly up-regulated genes (Fold hange 13, p-value <0.05) in IPF lungs. This finding was confirmed at the mRNA level by nCounter (R) expression analysis in additional 115 IPF lungs and 154 control lungs as well as at the protein level by western blot analysis. Immunohistochemical analysis revealed that COMP was expressed in dense fibrotic regions of IPF lungs and co-localized with vimentin and around pSMAD3 expressing cells. Stimulation of normal human lung fibroblasts with TGF-beta 1 induced an increase in COMP mRNA and protein expression. Silencing COMP in normal human lung fibroblasts significantly inhibited cell proliferation and negatively impacted the effects of TGF-beta 1 on COL1A1 and PAl1. COMP protein concentration measured by ELISA assay was significantly increased in serum of IPF patients compared to controls. Analysis of serum COMP concentrations in 23 patient who had prospective blood draws revealed that COMP levels increased in a time dependent fashion and correlated with declines in force vital capacity (FVC). Taken together, our results should encourage more research into the potential use of COMP as a biomarker for disease activity and TGF-beta 1 activity in patients with IPF. Hence, studies that explore modalities affect COMP expression, alleviate extracellular matrix rigidity and lung restriction in IPF and interfere with the amplification TGF-beta 1 signaling should be persuaded