LTBP2 is secreted from lung myofibroblasts and is a potential biomarker for idiopathic pulmonary fibrosis

Although differentiation of lung fibroblasts into α-smooth muscle actin (αSMA)-positive myofibroblasts is important in the progression of idiopathic pulmonary fibrosis (IPF), few biomarkers reflecting the fibrotic process have been discovered. We performed microarray analyses between FACS-sorted steady-state fibroblasts (lineage [CD45, TER-119, CD324, CD31, LYVE-1, and CD146]-negative and PDGFRα-positive cells) from untreated mouse lungs and myofibroblasts (lineage-negative, Sca-1-negative, and CD49e-positive cells) from bleomycin-treated mouse lungs. Among several genes upregulated in the FACS-sorted myofibroblasts, we focused on Ltbp2 , the gene encoding latent transforming growth factor-β binding protein-2 (LTBP2), because of the signal similarity to Acta2 , which encodes αSMA, in the clustering analysis. The upregulation was reproduced at the mRNA and protein levels in human lung myofibroblasts induced by transforming growth factor-β1. LTBP2 staining in IPF lungs was broadly positive in the fibrotic interstitium, mainly as an extracellular matrix protein; however, some of the αSMA-positive myofibroblasts were also stained. Serum LTBP2 concentrations, evaluated using ELISA, in IPF patients were significantly higher than those in healthy volunteers (mean: 21.4 ng/mL vs 12.4 ng/mL) and showed a negative correlation with % predicted forced vital capacity (r = –0.369). The Cox hazard model demonstrated that serum LTBP2 could pred...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research