title: Inhibitory effect of receptor for advanced glycation end products (RAGE) on the TGF-β-induced alveolar epithelial to mesenchymal transition.
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-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.
authors: Department of Internal Medicine, Yeouido St. Mary's Hospital, The Catholic University of Korea, School of Medicine, Seoul 150-713, Korea. jssong@catholic.ac.kr
authors: Jeong Sup
authors: JS
authors: Song
authors: Chun Mi
authors: CM
authors: Kang
authors: Chan Kwon
authors: CK
authors: Park
authors: Hyung Kyu
authors: HK
authors: Yoon
authors: Sook Young
authors: SY
authors: Lee
authors: Joong Hyun
authors: JH
authors: Ahn
authors: Hwa-Sik
authors: HS
authors: Moon
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000166:cytology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D016212:Transforming Growth Factor beta