Cartilage Oligomeric Matrix Protein in Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and life threatening disease with median survival of 2.5–3 years. The IPF lung is characterized by abnormal lung remodeling, epithelial cell hyperplasia, myofibroblast foci formation, and extracellular matrix deposition. Analysis of gene expression microarray data revealed that cartilage oligomeric matrix protein (COMP), a non-collagenous extracellular matrix protein is among the most significantly up-regulated genes (Fold change 13, p-value <0.05) in IPF lungs. This finding was confirmed at the mRNA level by nCounter® 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-β1 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-β1 on COL1A1 and PAI1. 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 patients 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-β1 activity in patients with IPF. Hence, studies that explore modalities that affect COMP expression, alleviate extracellular matrix rigidity and lung restriction in IPF and interfere with the amplification of TGF-β1 signaling should be persuaded.

Moraxella catarrhalis Evades Host Innate Immunity via Targeting Cartilage Oligomeric Matrix Protein

“…GDS1252; http://www.ncbi. nlm.nih.gov/geo/download/?acc=GDS1252) (37,38). We detected a wide distribution of COMP in lung tissues from two tested donors, one of whom was a diabetic, and the other was an alcoholic.…”

Cartilage oligomeric matrix protein participates in the pathogenesis of liver fibrosis

“…Increased COMP has been associated with fibrogenesis in systemic sclerosis [18], skin keloids [19, 20], vascular atherosclerosis [21], lung fibrosis [22] and chronic pancreatitis [23] as well as with other conditions such as rheumatoid arthritis [24, 25], osteoarthritis [26, 27], pseudoachondroplasia [28], acute trauma [29] and systemic lupus erythematosus [30, 31]. Recently, COMP has been proposed as a novel non-invasive marker for assessing cirrhosis and the risk of hepatocellular carcinoma [32] and as a biomarker of liver fibrosis in chronic hepatitis C [33].…”

Expression dynamics of caveolin-1 in fibroblasts of newborn rats with chronic lung disease and its impact on lung fibroblast proliferation

“…Pulmonary fibrosis is associated with excessively proliferating LFs that deposit in the interstitial lung or replace the normal lung epithelium 14 . LF hyper proliferation is a characteristic of CLD pulmonary fibrosis 15 .…”