Exploring the roles of extracellular matrix and cellular dysfunction in driving skin and pulmonary fibrosis

Skin and lung fibrosis have different aetiologies but share common features, including fibroblast activation and excess deposition of extracellular matrix (ECM). This thesis used polyacrylamide hydrogel cell culture models and ribonucleic acid sequencing (RNA-seq) to investigate the impact of ECM on fibroblasts and the molecular and cellular drivers common to skin and pulmonary fibrosis. Results demonstrated that fibrotic fibroblasts lose their sensitivity to matrix stiffness. Common genes and signalling pathways were dysregulated in both skin and pulmonary fibrosis. Finally, viral infection and impaired epithelial barrier function were identified as having a potential role in skin and lung fibrosis.