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Glucocorticoid receptor signalling contributes to muscle atrophy caused by acute inflammation
Author(s) -
Adams Olivia Joan,
Haegens Astrid,
Hermans Rob,
Kelders Marco,
Snepvangers Frank,
Schols Annemie,
Langen Ramon
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb582
Subject(s) - muscle atrophy , inflammation , endocrinology , glucocorticoid receptor , medicine , atrophy , skeletal muscle , glucocorticoid , lipopolysaccharide
Skeletal muscle atrophy accompanies acute inflammatory conditions including ARDS, COPD exacerbations and sepsis, and closely correlates with increased mortality. Increased circulating glucocorticoid levels have been linked to muscle atrophy. Nevertheless, the contribution of glucocorticoid receptor (GR) signalling to muscle atrophy caused by acute inflammation remains to be elucidated. To investigate this, acute pulmonary inflammation was induced by intra‐tracheal lipopolysaccharide (IT‐LPS) installation, in muscle‐specific GR knockout (MLC‐Cre+/− GR‐LoxP) and control (GR‐LoxP) mice. Circulating corticosterone levels were increased within 24h in response to IT‐LPS. Increased expression of mRNA transcripts encoding glutamine synthetase and phosphoenolpyruvate carboxykinase, as well as Atrogin1 and MuRF1, was detected in skeletal muscle of control mice following IT‐LPS, suggestive of GR‐ and atrophy signalling. Importantly, the reduction in body and muscle weight following IT‐LPS observed in GR‐LoxP control mice, was strongly attenuated in muscle‐specific GR knockout mice. These data implicate an important role for muscle GR‐signaling in muscle atrophy following acute (pulmonary) inflammation. This study was supported by the Dutch Top Institute Pharma (project # T1–201).