title: RAGE and tobacco smoke: insights into modeling chronic obstructive pulmonary disease.
abstract: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and airspace remodeling, leading to airflow limitation that is not completely reversible. Smoking is the leading risk factor for compromised lung function stemming from COPD pathogenesis. First- and second-hand cigarette smoke contain thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic lung inflammation and destructive alveolar remodeling. Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors primarily expressed by diverse lung cells. RAGE expression increases following cigarette smoke exposure and expression is elevated in the lungs of patients with COPD. RAGE is responsible in part for inducing pro-inflammatory signaling pathways that culminate in expression and secretion of several cytokines, chemokines, enzymes, and other mediators. In the current review, new transgenic mouse models that conditionally over-express RAGE in pulmonary epithelium are discussed. When RAGE is over-expressed throughout embryogenesis, apoptosis in the peripheral lung causes severe lung hypoplasia. Interestingly, apoptosis in RAGE transgenic mice occurs via conserved apoptotic pathways also known to function in advanced stages of COPD. RAGE over-expression in the adult lung models features of COPD including pronounced inflammation and loss of parenchymal tissue. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of COPD.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University Provo, UT, USA.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Robinson
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Stogsdill
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Lewis
authors.forename: Tyler T
authors.initials: TT
authors.lastname: Wood
authors.forename: Paul R
authors.initials: PR
authors.lastname: Reynolds