Antifibrotic properties of receptor for advanced glycation end products in idiopathic pulmonary fibrosis

• Published in: Pulmonary pharmacology & therapeutics Vol. 35; pp. 34 - 41
• Main Authors: Ding, Hui, Ji, XiuHai, Chen, Ruhua, Ma, Tieliang, Tang, Zhiwei, Fen, Yan, Cai, Hourong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2015
• Subjects: Actins - biosynthesis; Actins - genetics; Animals; Bleomycin; Collagen Type I - biosynthesis; EMT; Epithelial-Mesenchymal Transition; ERK; Humans; Idiopathic Pulmonary Fibrosis - chemically induced; Idiopathic Pulmonary Fibrosis - genetics; Idiopathic Pulmonary Fibrosis - pathology; IPF; MAP Kinase Signaling System - drug effects; Medical Education; Mice; Mice, Knockout; Phosphorylation - drug effects; Phosphorylation - genetics; Pulmonary/Respiratory; RAGE; Receptor for Advanced Glycation End Products - antagonists & inhibitors; Receptor for Advanced Glycation End Products - biosynthesis; Receptor for Advanced Glycation End Products - genetics; Signal Transduction - drug effects; TGF-β1; Transforming Growth Factor beta - pharmacology; TGF-β1; RAGE; EMT; IPF; ERK
• ISSN: 1094-5539; 1522-9629
• DOI: 10.1016/j.pupt.2015.10.010

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.