Smoking induced muscle dysfunction: unravelling the mechanisms leading to diminished regeneration

Bin Haidar, H. M. (2025) Smoking induced muscle dysfunction: unravelling the mechanisms leading to diminished regeneration. PhD thesis, University of Reading. doi: 10.48683/1926.00127818

Abstract/Summary

With an estimated 1 billion smokers worldwide, cigarette smoke is the leading cause of cancer and cardiovascular disease. Cigarette smoke has been found to cause weakness and wasting of skeletal muscle, the mechanism of which is still not completely understood. Recently, electronic cigarette use has become prominent worldwide. Consumption has been linked with multiple respiratory diseases but the effect on muscle is still not fully known. We hypothesize that cigarette smoke and vaping causes incomplete regeneration of muscle after acute damage. The aim of the project is to understand how cigarette smoke media (CSM) and vape media (VM) affects the growth, survival and regeneration of muscle by investigating the direct effect on immortalized myoblasts and mouse models. Then using gene expression along with a bio-informatic approach called “connectivity-mapping”, identify compounds that could be repurposed as therapies to promote muscle growth and function in smokers. Here we found that CSM reduced viability in several cell lines, reduced the migratory abilities of myoblasts and caused atrophy in myotubes. Both CSM and VM increased senescence, reduced fusion, induced organellar stress and dysregulated cytokine levels in vitro. In vivo CSM and VM did not affect animal weights, muscle weights, fibre cross sectional area or cause fibrosis after acute damage. However, they prolonged regeneration, and dysregulated cytokine levels. The gene expression data of CSM revealed several differentially expressed genes. The expression data was introduced into the C-map which identified harmine and asiaticoside as compounds that could potentially reverse the effects of CSM on muscle. We found that these compounds failed to rescue cells in a viability assay, therefore suggest a combination of transcriptomics and proteomics as a more robust solution to find alternatives.

Item Type	Thesis (PhD)
URI	https://centaur.reading.ac.uk/id/eprint/127818
Identification Number/DOI	10.48683/1926.00127818
Divisions	Life Sciences > School of Biological Sciences
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