Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/111166
Title: A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD
Author: Davidsen, Peter K.
Herbert, John M.
Antczak, Philipp
Clarke, Kim
Ferrer, Elisabet
Peinado, Víctor Ivo
Gonzalez, Constancio
Roca Torrent, Josep
Egginton, Stuart
Barberà i Mir, Joan Albert
Falciani, Francesco
Keywords: Malalties pulmonars obstructives cròniques
Sistemes biològics
Múscul llis
Comorbiditat
Fum
Rates (Animals de laboratori)
Chronic obstructive pulmonary diseases
Biological systems
Smooth muscle
Comorbidity
Smoke
Rats as laboratory animals
Issue Date: 9-Aug-2014
Publisher: BioMed Central
Abstract: BACKGROUND: A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology. Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting. METHODS: We have used a systems biology approach to compare the transcriptional profile of hindlimb skeletal muscles from a Guinea pig rodent model exposed to CS and/or chronic hypoxia to COPD patients with muscle wasting. RESULTS: We show that guinea pigs exposed to long-term CS accurately reflect most of the transcriptional changes observed in dysfunctional limb muscle of severe COPD patients when compared to matched controls. Using network inference, we could then show that the expression profile in whole lung of genes encoding for soluble inflammatory mediators is informative of the molecular state of skeletal muscles in the guinea pig smoking model. Finally, we show that CXCL10 and CXCL9, two of the candidate systemic cytokines identified using this pre-clinical model, are indeed detected at significantly higher levels in serum of COPD patients, and that their serum protein level is inversely correlated with the expression of aerobic energy metabolism genes in skeletal muscle. CONCLUSIONS: We conclude that CXCL10 and CXCL9 are promising candidate inflammatory signals linked to the regulation of central metabolism genes in skeletal muscles. On a methodological level, our work also shows that a system level analysis of animal models of diseases can be very effective to generate clinically relevant hypothesis.
Note: Reproducció del document publicat a: https://doi.org/10.1186/s13073-014-0059-5
It is part of: Genome Medicine, 2014, vol. 6, num. 8, p. 59
Related resource: https://doi.org/10.1186/s13073-014-0059-5
URI: http://hdl.handle.net/2445/111166
ISSN: 1756-994X
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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