Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.693891
Title: Transcriptional and translational control of muscle cell phenotype
Author: Lewis, Amy
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Abstract:
In adults, skeletal muscle retains a high degree of plasticity and continues to remodel in response to functional demand (e.g. exercise), by regulating its size (or mass) and fibre-type composition. Muscle atrophy and changes in fibre-type proportions can also occur as a result of disease, e.g. chronic obstructive pulmonary disease. COPD is defined by its effects on the lung however, skeletal muscle atrophy and a slow-to-fast fibre shift are common clinical observations, which are associated with reduced survival and exercise intolerance, making the molecular pathways that regulate these processes of interest. MicroRNAs (miRNAs) are small non-coding RNAs that reduce mRNA half-life and translation. Muscle-specific 'myomirs' contribute to the regulation of muscle phenotype and gene expression. In this thesis, the role of these miRNAs was investigated in the quadriceps of COPD patients; miR-1 and miR-499 were reduced in patients compared to controls. Low levels of miR-1 were associated with a low fat-free mass index (FFMI), while the reduction in miR-499 mirrored loss of type-1 fibres. Upstream regulators of miR-1 and miR-499, e.g. serum response factor (SRF), were also lower in patients relative to controls, whereas the downstream target of miR-1, HDAC4 was increased. A miRNA gene expression array also identified reduced expression of stem cell-associated miRNAs, derived from a miRNA cluster on chromosome 19 (C19MC), in COPD patients with a low FFMI; these patients also had fewer regenerating fibres, consistent with a loss of muscle mass. Together, these data imply that muscle atrophy in COPD is associated with altered miRNA expression and a reduced regenerative capacity.
Supervisor: Hopkinson, Nick ; Kemp, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.693891  DOI: Not available
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