Molecular mechanisms underlying COPD-muscle dysfunction unveiled through a systems medicine approach.
Bioinformatics
; 33(1): 95-103, 2017 01 01.
Article
em En
| MEDLINE
| ID: mdl-27794560
ABSTRACT
MOTIVATION Skeletal muscle dysfunction is a systemic effect in one-third of patients with chronic obstructive pulmonary disease (COPD), characterized by high reactive-oxygen-species (ROS) production and abnormal endurance training-induced adaptive changes. However, the role of ROS in COPD remains unclear, not least because of the lack of appropriate tools to study multifactorial diseases. RESULTS:
We describe a discrete model-driven method combining mechanistic and probabilistic approaches to decipher the role of ROS on the activity state of skeletal muscle regulatory network, assessed before and after an 8-week endurance training program in COPD patients and healthy subjects. In COPD, our computational analysis indicates abnormal training-induced regulatory responses leading to defective tissue remodeling and abnormal energy metabolism. Moreover, we identified tnf, insr, inha and myc as key regulators of abnormal training-induced adaptations in COPD. The tnf-insr pair was identified as a promising target for therapeutic interventions. Our work sheds new light on skeletal muscle dysfunction in COPD, opening new avenues for cost-effective therapies. It overcomes limitations of previous computational approaches showing high potential for the study of other multi-factorial diseases such as diabetes or cancer. CONTACT jroca@clinic.ub.es or martacascante@ub.eduSupplementary information Supplementary data are available at Bioinformatics online.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
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Músculo Esquelético
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Doença Pulmonar Obstrutiva Crônica
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Biologia de Sistemas
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Metabolismo Energético
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article