A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD

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RECERCAT Home > Universitat de Barcelona > IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer > Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) > View document

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dc.contributor.author	Davidsen, Peter K.
dc.contributor.author	Herbert, John M.
dc.contributor.author	Antczak, Philipp
dc.contributor.author	Clarke, Kim
dc.contributor.author	Ferrer, Elisabet
dc.contributor.author	Peinado Cabré, Víctor Ivo
dc.contributor.author	Gonzalez, Constancio
dc.contributor.author	Roca Torrent, Josep
dc.contributor.author	Egginton, Stuart
dc.contributor.author	Barberà i Mir, Joan Albert
dc.contributor.author	Falciani, Francesco
dc.date	2017-05-17T11:29:02Z
dc.date	2017-05-17T11:29:02Z
dc.date	2014-08-09
dc.date	2017-05-17T11:29:02Z
dc.identifier	1756-994X
dc.identifier	643845
dc.identifier	25228925
dc.identifier.uri	http://hdl.handle.net/2445/111166
dc.description	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.
dc.format	16 p.
dc.format	application/pdf
dc.language	eng
dc.publisher	BioMed Central
dc.relation	Reproducció del document publicat a: https://doi.org/10.1186/s13073-014-0059-5
dc.relation	Genome Medicine, 2014, vol. 6, num. 8, p. 59
dc.relation	https://doi.org/10.1186/s13073-014-0059-5
dc.rights	cc-by (c) Davidsen, Peter K. et al., 2014
dc.rights	http://creativecommons.org/licenses/by/3.0/es
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Malalties pulmonars obstructives cròniques
dc.subject	Sistemes biològics
dc.subject	Múscul llis
dc.subject	Comorbiditat
dc.subject	Fum
dc.subject	Rates (Animals de laboratori)
dc.subject	Chronic obstructive pulmonary diseases
dc.subject	Biological systems
dc.subject	Smooth muscle
dc.subject	Comorbidity
dc.subject	Smoke
dc.subject	Rats as laboratory animals
dc.title	A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/publishedVersion

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