title: Plausible Roles for RAGE in Conditions Exacerbated by Direct and Indirect (Secondhand) Smoke Exposure.
abstract: Approximately 1 billion people smoke worldwide, and the burden placed on society by primary and secondhand smokers is expected to increase. Smoking is the leading risk factor for myriad health complications stemming from diverse pathogenic programs. First- and second-hand cigarette smoke contains thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic inflammatory responses and destructive remodeling events. In the current review, we outline details related to compromised pulmonary and systemic conditions related to smoke exposure. Specifically, data are discussed relative to impaired lung physiology, cancer mechanisms, maternal-fetal complications, cardiometabolic, and joint disorders in the context of smoke exposure exacerbations. As a general unifying mechanism, the receptor for advanced glycation end-products (RAGE) and its signaling axis is increasingly considered central to smoke-related pathogenesis. RAGE is a multi-ligand cell surface receptor whose expression increases following cigarette smoke exposure. RAGE signaling participates in the underpinning of inflammatory mechanisms mediated by requisite cytokines, chemokines, and remodeling enzymes. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of lung disease and systemic complications that combine during the demise of those exposed.
authors.affiliation: Lung and Placenta Research Laboratory, Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA. jblewis1101@gmail.com.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Lewis
authors.affiliation: Lung and Placenta Research Laboratory, Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA. kelseyhirschi.6@gmail.com.
authors.forename: Kelsey M
authors.initials: KM
authors.lastname: Hirschi
authors.affiliation: Lung and Placenta Research Laboratory, Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA. jarroyo@byu.edu.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Arroyo
authors.affiliation: Laboratory of Obesity and Metabolism, Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA. benjbnikman@byu.edu.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Bikman
authors.affiliation: Laboratory of Osteoarthritis and Inflammatory Diseases, Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA. davidlkooyman@byu.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Kooyman
authors.affiliation: Lung and Placenta Research Laboratory, Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA. paul_reynolds@byu.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000378:metabolism*; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology / Q000378:metabolism*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects
chemical_list: D017127:Glycation End Products, Advanced; D014028:Tobacco Smoke Pollution
keywords: disease; exposure; receptor for advanced glycation end-products (RAGE); secondhand smoke