Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.656381
Title: TGF-beta family ligands in autophagy and muscle wasting
Author: Lee, Jen Yee
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Abstract:
Chronic Obstructive Pulmonary Disease (COPD) is a collective term for emphysema, chronic bronchitis, and obstructive bronchiolitis, which is caused by chronic tobacco smoke exposure. COPD is a multi-system disease; skeletal muscle is one such system that is dysfunctional in a significant proportion of COPD patients. Muscle weakness and wasting is observed in COPD patients, with fibre type changes as well as fibre atrophy reported. Skeletal muscle as a target for pharmacotherapy in COPD as exercise training improves life expectancy and quality of life in patients. Loss of protein contributes to muscle atrophy; however, the mechanisms and signalling pathways involved in protein degradation are not fully understood. Autophagy is a protein degradation pathway implicated in muscle atrophy. Additionally, the TGF-β superfamily member -myostatin and FHL1 are signalling molecules of interest. The cytokine myostatin is a recognised inhibitor of muscle growth, whilst FHL1 is an adaptor protein usually associated with hypertrophy in muscle. The data presented herein focuses on three aspects: the effect of myostatin on autophagy, the interaction between myostatin and FHL1 in atrophy and the effect of smoke exposure on autophagy. Furthermore, the effects of other atrophy associated signalling molecules (growth differentiation factor 15, GDF-15 and angiotensin-II, ang-II) on these themes were examined. The data show that myostatin is a novel inducer of autophagy indicating that myostatin can induce protein degradation through autophagy. FHL1 augmented myostatin induced signalling in vitro and in vivo, suggesting a potential mechanism by which type II fibres are more susceptible to atrophy than others and helping to account for the fibre type changes and atrophy in COPD. The role of smoke exposure of autophagy remains unclear; however, GDF-15 may be involved in muscle atrophy. Ang-II did not induce autophagy in vivo and inhibition of angiotensin signalling had no effect on autophagy in COPD patients.
Supervisor: Kemp, Paul; Hopkinson, Nick Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.656381  DOI: Not available
Share: