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

Markus A. Queisser, Fotini M. Kouri, Melanie Königshoff, Malgorzata Wygrecka, Uwe Schubert, Oliver Eickelberg, Klaus T. Preissner

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

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 downregulation 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 small interfering RNA-induced knockdown of RAGE increased cell proliferation and migration of A549 cells and human primary fibroblast in vitro. These results indicate that RAGE serves a protective role in the lung, and that loss of the receptor is related to functional changes of pulmonary cell types, with the consequences of fibrotic disease.

Original languageEnglish (US)
Pages (from-to)337-345
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume39
Issue number3
DOIs
StatePublished - Sep 1 2008

Keywords

  • Adhesion molecule
  • Alveolar epithelial cells
  • Idiopathic pulmonary fibrosis
  • Pulmonary fibrosis
  • Receptor for advanced glycation end products

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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