title: Antifibrotic properties of receptor for advanced glycation end products in idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive chronic interstitial lung disease with poor survival. Previous reports suggested the contributory effect of receptor for advanced glycation end products (RAGE) to the pathogenesis of IPF. But the findings are controversial. The present in vivo study with RAGE null mice, we further confirmed the evidence that lack of RAGE evolves worse bleomycin-induced pulmonary fibrosis compared with control mice. Moreover, RAGE null mice spontaneously developed similar pathogenesis of lung fibrosis via immunohistochemical staining. In addition, we investigated the negative roles of RAGE on epithelial-mesenchymal transition (EMT) indicated by elevated α-smooth muscle actin (α-SMA) and collagen-I (Col-I) deposition in A549 cell treated with transforming growth factor-β (TGF-β), all of which were blocked by sRAGE, a decoy receptor. Furthermore, interacting with the specific ligand as AGE, RAGE blocked TGF-β-induced activation of Smad2, ERK and JNK signals in A549 cells, which were also challenged by sRAGE administration. This present study confirmed an important role of RAGE in vivo and vitro models of pulmonary fibrosis and suggested the therapeutic possibility for pulmonary fibrosis via RAGE regulation.
authors.affiliation: Department of Pulmonary Medicine, Affiliated Yixing People Hospital, Jiangsu University, 214200, China. Electronic address: dh1350519@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Oncology, Affiliated Taicang Hospital of Traditional Chinese Medicine, Suzhou, China.
authors.forename: XiuHai
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Pulmonary Medicine, Affiliated Yixing People Hospital, Jiangsu University, 214200, China.
authors.forename: Ruhua
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Pulmonary Medicine, Affiliated Yixing People Hospital, Jiangsu University, 214200, China.
authors.forename: Tieliang
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Pulmonary Medicine, Affiliated Yixing People Hospital, Jiangsu University, 214200, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Pulmonary Medicine, Affiliated Yixing People Hospital, Jiangsu University, 214200, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fen
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, 210029, China.
authors.forename: Hourong
authors.initials: H
authors.lastname: Cai
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001761:Bleomycin; D024042:Collagen Type I / Q000096:biosynthesis; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D000199:Actins; D024042:Collagen Type I; D000067759:Receptor for Advanced Glycation End Products; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse; D001761:Bleomycin
keywords: EMT; ERK; IPF; RAGE; TGF-β1