FHL1 activates myostatin signalling in skeletal muscle and promotes atrophy
File(s)Lee et al myostatin FHL1 for FEBSopen R2 CLEAN_Part2.pdf (33.37 MB)
Supporting information
Author(s)
Kemp, P
Lee, JY
lori, O
Wells, D
Type
Journal Article
Abstract
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.
Abbreviations
FHL1, four and a half LIM domain protein 1; COPD, chronic obstructive pulmonary disease; TGF-β, transforming growth factor beta; MHC, myosin heavy chain; GDF-15, growth and differentiation factor 15; PAI-1, plasminogen activator inhibitor 1; TA, tibialis anterior; VEGF-C, vascular endothelial growth factor C
Abbreviations
FHL1, four and a half LIM domain protein 1; COPD, chronic obstructive pulmonary disease; TGF-β, transforming growth factor beta; MHC, myosin heavy chain; GDF-15, growth and differentiation factor 15; PAI-1, plasminogen activator inhibitor 1; TA, tibialis anterior; VEGF-C, vascular endothelial growth factor C
Date Issued
2015-09-01
Date Acceptance
2015-08-25
Citation
FEBS Open Bio, 2015, 5, pp.753-762
ISSN
2211-5463
Publisher
Elsevier
Start Page
753
End Page
762
Journal / Book Title
FEBS Open Bio
Volume
5
Copyright Statement
© 2015 The Authors. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Subjects
Muscle wasting
Fibre type
FHL1
Myostatin
Mouse
Publication Status
Published