Fibroblasts are well known to be the key cell involved in the production of extracellular matrix in normal skin, wound repair and in scars and fibrotic disease. However all fibroblasts are not equal and there are likely specific subpopulations that contribute differentially to tissue homeostasis and disease. Similarly, whilst fibroblasts are critical to matrix production, so the matrix environment can significantly influence fibroblast phenotype and promote fibrotic responses. This is critical in the process of injury repair and can lead to deleterious positive feedback loops in progressive fibrosis.
We have investigated cellular and molecular changes in fibroblast phenotype that impact on matrix production and the response to matrix in human cells using single cell sequencing, metabolic tracing and in vitro phenotypic assays. Differences in matrix dynamics between normal skin and scar/fibrotic tissue are underpinned by changes to fibroblast phenotype. Similarly the changes in matrix structure appear to be important in the disruption to fibroblast activity. This work will contribute to an increased understanding of the changes underlying scarring and fibrotic disease, with the potential to facilitate new interventions to improve patient outcomes and reduce the burden of fibrosis.