Fibroblast heterogeneity in physiological conditions and fibrotic disease

Inflammation and tissue injury are strong stimuli for fibroblast activation and initiation of reparative processes. In certain disease states, pathological fibrosis occurs. Fibroblasts isolated from these diseased tissues often display a persistently abnormal phenotype characterized by increased synthesis of matrix components such as collagen. This metabolic abnormality is apparently independent of continued exposure to any pathological stimulus that may have initiated the process. Since fibroblasts are heterogenous in proliferative capacity, in synthesis of collagen and other matrix proteins and in response to immune mediators and growth factors, clonal selection, i.e. selective increase in fibroblast subpopulations, may explain the long-term effects of acute in vivo activation on fibroblast behavior. Studies of SSc fibroblasts are consistent with clonal selection and/or clonal activation, processes that may play an important role in fibrosis in this and other disorders.