Figure 1

The cellular origins of pathogenic 'activated' fibroblasts in scleroderma. Scleroderma (SSc) fibrosis is characterised by the excessive accumulation of extracellular matrix (ECM) proteins, including type I and type III collagen, by 'activated fibroblasts' or myofibroblasts and leads to the development of pathological scaring and loss of organ function. These cells arise from a differentiation of resident and recruited circulating progenitor cells and collectively are likely to contribute the myofibroblast population. Myofibroblasts have been shown to arise from a number of cellular sources through the differentiation and activation of tissue-resident cells: epithelial to mesenchymal transition; endothelial to mesenchymal transition; fibroblast to myofibroblast transition; pericyte to mesenchymal transition; smooth muscle cell differentiation. In addition the recruitment and differentiation of circulating bone marrow-derived cells (BMDC) and fibrocytes can contribute to the myofibroblast population. SSc fibroblasts also promote a pro-fibrotic microenvironment, secreting growth factors, chemokines and cytokines that can in turn act on resident and infiltrating cells in an autocrine and paracrine manner to expand the reservoir of pro-fibrotic fibroblasts present in SSc fibrotic lesions.