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Modulation of nuclear receptor activity by FHL proteins in the regulation of muscle mass and phenotype

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Title: Modulation of nuclear receptor activity by FHL proteins in the regulation of muscle mass and phenotype
Authors: Lori, Oritseundede Dede
Item Type: Thesis or dissertation
Abstract: Skeletal muscle wasting or atrophy is an important public health problem associated with aging and a number of mortality related diseases including, chronic obstructive pulmonary disease and cancer. Muscle wasting is a reflection of an imbalance in the regulation of muscle mass and phenotype and is controlled by a number of factors in mammals including the level of physical activity, hormonal status and the activity of signaling molecules and pathways. The aim of this thesis was therefore to understand better the muscle wasting pathway by focusing on the four-and-a-half lim protein family of which one member has been shown to be a key regulator of muscle mass (FHL1). Results showed that FHL1 could cause an increase and decrease in myotube size in a skeletal muscle cell line by increasing hormone activity through activating the AR and GR respectively. Furthermore over-expression of FHL1 in the tibialis anterior (TA) muscle of mice caused hypertrophy in the absence of dexamethasone treatment, however this muscle phenotype was negated by treatment of the mice with dexamethasone. Another family member named FHL3, investigated due to its high expression in skeletal muscle was found to alter AR and GR activity in vitro, however these observations did not translate to in vivo results as, unlike the effects of FHL1 on muscle size, there was no increase in the size of TA muscles over-expressing FHL3 nor did dexamethasone treatment of FHL3 expressing muscles cause a significant reduction in muscle size compared to TA muscles extracted from saline treated muscles. Together these data support FHL1 as a key regulator of skeletal muscle mass and phenotype.
Content Version: Open Access
Issue Date: Jun-2015
Date Awarded: Oct-2015
URI: http://hdl.handle.net/10044/1/54453
DOI: https://doi.org/10.25560/54453
Supervisor: Kemp, Paul
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (Great Britain)
GlaxoSmithKline
Department: National Heart and Lung Institute
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:National Heart and Lung Institute PhD theses



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