Exp Mol Med.  2011 Sep;43(9):517-524. 10.3858/emm.2011.43.9.059.

Inhibitory effect of receptor for advanced glycation end products (RAGE) on the TGF-beta-induced alveolar epithelial to mesenchymal transition

• Song JS
• Kang CM
• Park CK
• Yoon HK
• Lee SY
• Ahn JH
• Moon HS

• KMID: 1022128
• DOI: http://doi.org/10.3858/emm.2011.43.9.059

Abstract

Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in most adult tissues except the lung. In this study, we evaluated the interaction of ligand advanced glycation end products (AGE) with RAGE during the epithelial to myofibroblast transition in rat AECs. Our results indicate that AGE inhibited the TGF-beta-dependent alveolar EMT by increasing Smad7 expression, and that the effect was abolished by RAGE siRNA treatment. Thus, the induction of Smad7 by the AGE-RAGE interaction limits the development of pulmonary fibrosis by inhibiting TGF-beta-dependent signaling in AECs.

Keyword

advanced glycosylation end-product receptor; epithelial-mesenchymal transition; glycosylation end products, advanced; pulmonary fibrosis; Smad7 protein

MeSH Terms

Animals
Epithelial Cells/cytology
Epithelial-Mesenchymal Transition/*drug effects
Glycosylation End Products, Advanced/genetics/*metabolism
Idiopathic Pulmonary Fibrosis/metabolism
Pulmonary Alveoli/cytology
RNA, Small Interfering/genetics
Rats
Receptors, Immunologic/genetics/*metabolism
Smad7 Protein/genetics/*metabolism
Transforming Growth Factor beta/genetics/metabolism