title: A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.
abstract: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.
authors: School of Biosciences, University of Birmingham, Birmingham, UK.
authors: Nil
authors: N
authors: Turan
authors: Susana
authors: S
authors: Kalko
authors: Anna
authors: A
authors: Stincone
authors: Kim
authors: K
authors: Clarke
authors: Ayesha
authors: A
authors: Sabah
authors: Katherine
authors: K
authors: Howlett
authors: S John
authors: SJ
authors: Curnow
authors: Diego A
authors: DA
authors: Rodriguez
authors: Marta
authors: M
authors: Cascante
authors: Laura
authors: L
authors: O'Neill
authors: Stuart
authors: S
authors: Egginton
authors: Josep
authors: J
authors: Roca
authors: Francesco
authors: F
authors: Falciani
mesh_terms: D000368:Aged; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D016207:Cytokines / Q000097:blood; D004734:Energy Metabolism; D005260:Female; D020869:Gene Expression Profiling; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D010101:Oxygen Consumption; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D049490:Systems Biology / Q000379:methods*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D006657:Histones; D053583:Interleukin-1beta; D012333:RNA, Messenger