FHL1 activates myostatin signalling in skeletal muscle and promotes atrophy.
Myostatin is a TGFβ family ligand that reduces muscle mass. In cancer cells, TGFβ signalling is increased by the protein FHL1. Consequently, FHL1 may promote signalling by myostatin. We therefore tested the ability of FHL1 to regulate myostatin function. FHL1 increased the myostatin activity on a SMAD reporter and increased myostatin dependent myotube wasting. In mice, independent expression of myostatin reduced fibre diameter whereas FHL1 increased fibre diameter, both consistent with previously identified effects of these proteins. However, co-expression of FHL1 and myostatin reduced fibre diameter to a greater extent than myostatin alone. Together, these data suggest that the expression of FHL1 may exacerbate muscle wasting under the appropriate conditions.
Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Jen Y
JY
Lee
Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Dede
D
Lori
Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
Dominic J
DJ
Wells
Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Paul R
PR
Kemp
COPD, chronic obstructive pulmonary disease; FHL1; FHL1, four and a half LIM domain protein 1; Fibre type; GDF-15, growth and differentiation factor 15; MHC, myosin heavy chain; Mouse; Muscle wasting; Myostatin; PAI-1, plasminogen activator inhibitor 1; TA, tibialis anterior; TGF-β, transforming growth factor beta; VEGF-C, vascular endothelial growth factor C