Figure 8

Convergence of microvascular pericytes and resident fibroblasts to a myofibroblast lineage in SSc. Two pathways potentially contribute to the fibrogenic response in dcSSc. Microvascular pericytes (Thy-1^+ve /α-SMA^+ve ) become activated as a result of microvascular damage and produce the ED-A splice variant of fibronectin, a protein known to induce the myofibroblast phenotype. The microvascular derived ED-A FN in concert with the actions TGF-β may also act upon resident perivascular fibroblasts (Thy-1^+ve /α-SMA^-ve ) stimulating their differentiation to myofibroblasts. Proliferation of both pericytes and fibroblasts may help to create a pool of potential myofibroblasts. α-SMA, alpha smooth muscle actin; dcSSc, diffuse cutaneous systemic sclerosis; ED-A FN, ED-A splice variant of fibronectin; TGF-β, transforming growth factor-beta.