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Article Dans Une Revue Scientific Reports Année : 2017

Muscle hypertrophy in hypoxia with inflammation is controlled by bromodomain and extra-terminal domain proteins

Résumé

Some of the Chronic Obstructive Pulmonary Disease (COPD) patients engaged in exercise-based muscle rehabilitation programs are unresponsive. To unravel the respective role of chronic hypoxia and pulmonary inflammation on soleus muscle hypertrophic capacities, we challenged male Wistar rats to repeated lipopolysaccharide instillations, associated or not with a chronic hypoxia exposure. Muscle hypertrophy was initiated by bilateral ablation of soleus agonists 1 week before sacrifice. To understand the role played by the histone acetylation, we also treated our animals with an inhibitor of bromodomains and extra terminal proteins (I-BET) during the week after surgery. Pulmonary inflammation totally inhibited this hypertrophy response under both normoxic and hypoxic conditions (26% lower than control surgery, p < 0.05), consistent with the S6K1 and myogenin measurements. Changes in histone acetylation and class IIa histone deacetylases expression, following pulmonary inflammation, suggested a putative role for histone acetylation signaling in the altered hypertrophy response. The I-BET drug restored the hypertrophy response suggesting that the non-response of muscle to a hypertrophic stimulus could be modulated by epigenetic mechanisms, including histone-acetylation dependant pathways. Drugs targeting such epigenetic mechanisms may open therapeutic perspectives for COPD patients with systemic inflammation who are unresponsive to rehabilitation.

Dates et versions

hal-01869973 , version 1 (07-09-2018)

Identifiants

Citer

Clovis Chabert, Saadi Khochbin, Sophie Rousseaux, Rebecca Furze, Nicholas Smithers, et al.. Muscle hypertrophy in hypoxia with inflammation is controlled by bromodomain and extra-terminal domain proteins. Scientific Reports, 2017, 7 (1), ⟨10.1038/s41598-017-12112-0⟩. ⟨hal-01869973⟩
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