Healing scars: targeting pericytes to treat fibrosis

Abstract

Fibrosis, with resultant loss of organ function, is the endpoint of many diseases. Despite this, no effective anti-fibrotic therapies exist. The myofibroblast is the key cell driving fibrosis but its origins remain controversial. A growing body of work provides strong evidence that the pericyte, a perivascular cell present throughout the microvasculature, is a major myofibroblast precursor in multiple tissues. This review summarizes the principle experimental and clinical evidence underpinning this conclusion and outlines strategies for targeting pericyte transdifferentiation during fibrogenesis. Successful targeting of pro-fibrogenic pericytes has the potential to halt or even reverse fibrosis and thus reduce the enormous worldwide healthcare burden that currently exists as a result of fibrotic disease.

Figure 1.

Following injury pericytes in multiple organs, including kidney, liver and skin, can migrate from their usual perivascular location and transdifferentiate into matrix-secreting myofibroblasts. Potential therapeutic targets to inhibit this process are shown. TGFβ, transforming growth factor beta; PDGFRβ, platelet-derived growth factor receptor beta; VEGFR2, vascular endothelial growth factor receptor 2; PPARγ, peroxisome proliferator-activated receptor gamma; CTGF, connective tissue growth factor.