Fig. 5

Summary of the cellular interactions in chronic inflammation leading to a decline in muscle growth. The incomplete switch from M1 to M2c results in a greater presence of M2b macrophages which present both impaired pro- and impaired anti-inflammatory properties, often resulting in enhanced deposition of ECM components, and impaired satellite cell function. This also results in a reduced presence of M2c macrophages. The mechanisms and pathways presented are based on chronic inflammatory microenvironments (proposed in RA), with blue indicating mechanisms confirmed in studies of RA. Different colours indicate different cell focus areas; green = muscle niche; purple = inflammatory system; red = fibroblasts and fibrosis. Increased signalling are indicated by double-line arrows, while dotted line arrows indicate decreased signalling. SCs  satellite cells, IGF  insulin-like growth factor, Murf-1  muscle ring finger protein-1, Mafbx  muscle atrophy f-box, exos  exosomes, Rrbp1  ribosome binding protein-1, IL  interleukin, TNF-α  tumor necrosis factor-α, IFN-γ interferon-γ, LPS  lipopolysaccharides, GM-CSF  granulocyte-monocyte colony-stimulating factor, TGF-β  transforming growth factor-β, TIMP  tissue inhibitor of metalloproteinase, MMP  matrix metalloproteinase, CTGF  connective tissue growth factor, FAPs  fibro-adipogenic progenitor cells, ECM  extracellular matrix, α-SMA  α-smooth muscle actin