Pericytes in tissue fibrosis

Pericytes are mural cells, embedded within the microvascular basement membrane and primarily involved in preservation of vessel integrity and regulation of vascular permeability and blood flow. Their study poses major challenges due to the absence of specific and reliable markers for their identification. Emerging evidence suggests that, in addition to their involvement in the regulation of microvascular responses, pericytes may also play a central role in repair, inflammation, and fibrosis in many different organs. Following injury, pericytes may dissociate from endothelial cells, acquiring inflammatory and profibrotic phenotypes. Fibrogenic activation of pericytes has been reported in many different pathologic conditions and may involve stimulation by inflammatory cytokines, transforming growth factor-β, or platelet-derived growth factor-BB. Activated pericytes may stimulate fibrosis by secreting fibroblast-activating growth factors, by producing proteins involved in extracellular matrix remodeling, and by depositing structural and matricellular matrix proteins. Conflicting findings have been reported on the phenotypic plasticity of pericytes and their capacity to convert to fibroblasts and myofibroblasts. Organ-specific differences in pericyte populations and differences in sensitivity and specificity of the pericyte fate mapping and fibroblast identification strategies may account for the conflicting observations reported in various studies. This review manuscript deals with the fate, role, and mechanisms of activation of pericytes in tissue fibrosis. We discuss both the general mechanisms of pericyte activation and the organ-specific roles of pericytes in fibrotic conditions involving the kidney, liver, lung, heart, and central nervous system. Understanding the role of pericytes is important to develop effective therapies for fibrotic conditions.