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Cartilage oligomeric matrix protein in idiopathic pulmonary fibrosis

Vuga, LJ and Milosevic, J and Pandit, K and Ben-Yehudah, A and Chu, Y and Richards, T and Sciurba, J and Myerburg, M and Zhang, Y and Parwani, AV and Gibson, KF and Kaminski, N (2013) Cartilage oligomeric matrix protein in idiopathic pulmonary fibrosis. PLoS ONE, 8 (12).

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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. © 2013 Vuga et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Vuga, LJlgv4@pitt.eduLGV4
Milosevic, Jjam206@pitt.eduJAM206
Pandit, K
Ben-Yehudah, A
Chu, Yyac20@pitt.eduYAC20
Richards, T
Sciurba, J
Myerburg, Mmmmst40@pitt.eduMMMST40
Zhang, Yzhang3@pitt.eduZHANG3
Parwani, AV
Gibson, KFkfg@pitt.eduKFG
Kaminski, N
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorWu, MinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Magee-Women's Research Institute
Date: 20 December 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0083120
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Date Deposited: 16 Jun 2014 16:25
Last Modified: 25 Jan 2019 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/21864

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