The pronounced high expression of discoidin domain receptor 2 in human interstitial lung diseases

Abstract

The most typical structural feature of human interstitial lung diseases (ILDs) is the accumulation of vast amounts of collagens within the lung interstitium. The membrane receptors that are responsible for recognising collagens and then transducing signals into the cells include four members of the integrin family (α1β1, α2β1, α10β1 and α11β1) and two members of the discoidin domain receptor family (DDR1 and DDR2). However, it remains unknown whether these six collagen receptors similarly contribute to the pathogenesis of fibrotic lung diseases. Quantitative real-time PCR (qPCR) was utilised to assess the mRNA expression of the genes studied. Immunoblot experiments were performed to analyse the protein abundance and kinase activity of the gene products. The tissue location was determined by immunohistochemical staining. qPCR data showed that DDR2 mRNA displays the most dramatic difference between idiopathic pulmonary fibrosis (IPF) patients and healthy groups. The outstanding increases in DDR2 proteins were also observed in some other types of ILD besides IPF. DDR2-expressing cells in ILD tissue sections were found to exhibit spindle or fibroblastic shapes. Our investigation suggests that DDR2 might represent a major cell surface protein that mediates collagen-induced cellular effects in human ILD and, hence, is suitable for their diagnosis and therapy.