title: Pathological changes in the COPD lung mesenchyme--novel lessons learned from in vitro and in vivo studies.
abstract: Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death worldwide and, in contrast to the trend for cardiovascular diseases, mortality rates still continue to climb. This increase is in part due to an aging population, being expanded by the "Baby boomer" generation who grew up when smoking rates were at their peak and by people in developing countries living longer. Sadly, there has been a disheartening lack of new therapeutic approaches to counteract the progressive decline in lung function associated with the disease that leads to disability and death. COPD is characterized by irreversible chronic airflow limitation that is caused by emphysematous destruction of lung elastic tissue and/or obstruction in the small airways due to occlusion of their lumen by inflammatory mucus exudates, narrowing and obliteration. These lesions are mainly produced by the response of the tissue to the repetitive inhalational injury inflicted by noxious gases, including cigarette smoke, which involves interaction between infiltrating inflammatory immune cells, resident cells (e.g. epithelial cells and fibroblasts) and the extra cellular matrix. This interaction leads to tissue destruction and airway remodeling with changes in elastin and collagen, such that the epithelial-mesenchymal trophic unit is dysregulated in both the disease pathologies. This review focuses on: 1--novel inflammatory and remodeling factors that are altered in COPD; 2--in vitro and in vivo models to understand the mechanism whereby the extra cellular matrix environment in altered in COPD; and 3--COPD in the context of wound-repair tissue responses, with a focus on the regulation of mesenchymal cell fate and phenotype.
authors.affiliation: Department of Physiology, University of Manitoba, and Canada Biology of Breathing Theme, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Ojo
authors.affiliation: Division of Respiratory Medicine and Nottingham Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, United Kingdom.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Lagan
authors.affiliation: University of Groningen, University Medical Centre, Groningen, Department of Pathology and Medical Biology, The Netherlands.
authors.forename: Vijayanand
authors.initials: V
authors.lastname: Rajendran
authors.affiliation: University of Groningen, University Medical Centre, Groningen, Department of Pathology and Medical Biology, The Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Spanjer
authors.affiliation: Woolcock Institute of Medical Research, Sydney, New South Wales, Australia; Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Shapingba, Chongqing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: NHMRC Centre of Research Excellence for Chronic Respiratory Disease and Lung Ageing, School of Medicine, University of Tasmania, Australia.
authors.forename: Sukhwinder Singh
authors.initials: SS
authors.lastname: Sohal
authors.affiliation: University of Groningen, University Medical Centre, Groningen, Department of Pathology and Medical Biology, The Netherlands.
authors.forename: Irene
authors.initials: I
authors.lastname: Heijink
authors.affiliation: Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
authors.forename: Robin
authors.initials: R
authors.lastname: Jones
authors.affiliation: Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL, USA.
authors.forename: Harm
authors.initials: H
authors.lastname: Maarsingh
authors.affiliation: Centre for Heart Lung Innovation and Department of Anesthesiology Pharmacology & Therapeutics, University of British Columbia, St Paul's Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. Electronic address: Tillie.Hackett@hli.ubc.ca.
authors.forename: Tillie L
authors.initials: TL
authors.lastname: Hackett
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000166:cytology / Q000473:pathology* / Q000503:physiopathology; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology* / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology
keywords: Chronic obstructive pulmonary disease; Epithelial–mesenchymal interactions; Extra cellular matrix; Inflammation; Novel pharmacological targets