Loss of RAGE in pulmonary fibrosis: molecular relations to functional changes in pulmonary cell types.

The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the Ig superfamily. While vascular RAGE expression is associated with kidney and liver fibrosis, high expression levels of RAGE are found under physiological conditions in the lung. In this study, RAGE expression in idiopathic pulmonary fibrosis was assessed, and the relationship of the receptor to functional changes of epithelial cells and pulmonary fibroblasts in the pathogenesis of the disease was investigated. Significant down-regulation of RAGE was observed in lung homogenate and alveolar epithelial type II cells from patients with idiopathic pulmonary fibrosis, as well as in bleomycin-treated mice, demonstrated by RT-PCR, Western blotting, and immunohistochemistry. In vitro, RAGE down-regulation was provoked by stimulation of primary human lung fibroblasts and A549 epithelial cells with the proinflammatory cytokines, transforming growth factor-β1 or TNF-α. Blockade of RAGE resulted in impaired cell adhesion, and s...