FHL1 activates myostatin signalling in skeletal muscle and promotes atrophy
| Autor: | Dede Lori, Paul R. Kemp, Jen Y. Lee, Dominic J. Wells |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
FHL1
four and a half LIM domain protein 1 medicine.medical_specialty FHL1 Mouse QH301-705.5 SMAD Myostatin Biology General Biochemistry Genetics and Molecular Biology Muscle wasting Atrophy Internal medicine Research article TGF-β transforming growth factor beta Myosin medicine Biology (General) PAI-1 plasminogen activator inhibitor 1 TA tibialis anterior Skeletal muscle Transforming growth factor beta VEGF-C vascular endothelial growth factor C medicine.disease musculoskeletal system medicine.anatomical_structure Endocrinology COPD chronic obstructive pulmonary disease GDF-15 growth and differentiation factor 15 Cancer cell biology.protein MHC myosin heavy chain Fibre type |
| Zdroj: | FEBS Open Bio FEBS Open Bio, Vol 5, Iss 1, Pp 753-762 (2015) |
| ISSN: | 2211-5463 |
| DOI: | 10.1016/j.fob.2015.08.011 |
| Popis: | Highlights • Myostatin signals via SMADs to promote muscle wasting. • FHL1 normally promotes hypertrophy but can activate SMAD signalling. • FHL1 promoted myostatin signalling in vitro. • FHL1 promoted hypertrophy in the absence of myostatin but atrophy in its presence. 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. |
| Databáze: | OpenAIRE |
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