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

• Published in: Experimental & molecular medicine Vol. 43; no. 9; pp. 517 - 524
• Main Authors: Song, Jeong Sup, Kang, Chun Mi, Park, Chan Kwon, Yoon, Hyung Kyu, Lee, Sook Young, Ahn, Joong Hyun, Moon, Hwa-Sik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.09.2011; Korean Society for Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Epithelial Cells - cytology; Epithelial-Mesenchymal Transition - drug effects; Glycation End Products, Advanced - genetics; Glycation End Products, Advanced - metabolism; Idiopathic Pulmonary Fibrosis - metabolism; Medical Biochemistry; Molecular Medicine; Original; Pulmonary Alveoli - cytology; Rats; Receptor for Advanced Glycation End Products; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; RNA, Small Interfering - genetics; Smad7 Protein - genetics; Smad7 Protein - metabolism; Stem Cells; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; 생화학; glycosylation end products, advanced; Smad7 protein; epithelial-mesenchymal transition; advanced glycosylation end-product receptor; pulmonary fibrosis
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.3858/emm.2011.43.9.059

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-β-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-β-dependent signaling in AECs.