[HTML][HTML] Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis

VS Rajkumar, K Howell, K Csiszar, CP Denton… - Arthritis research & …, 2005 - Springer
VS Rajkumar, K Howell, K Csiszar, CP Denton, CM Black, DJ Abraham
Arthritis research & therapy, 2005Springer
The mechanisms by which microvascular damage leads to dermal fibrosis in diffuse
cutaneous systemic sclerosis (dcSSc) are unclear. We hypothesized that microvascular
pericytes constitute a cellular link between microvascular damage and fibrosis by
transdifferentiating into myofibroblasts. We used a combination of immunohistochemistry
and double immunofluorescence labelling of frozen skin biopsies taken from normal and
dcSSc patients to determine whether a phenotypic link between pericytes and …
Abstract
The mechanisms by which microvascular damage leads to dermal fibrosis in diffuse cutaneous systemic sclerosis (dcSSc) are unclear. We hypothesized that microvascular pericytes constitute a cellular link between microvascular damage and fibrosis by transdifferentiating into myofibroblasts. We used a combination of immunohistochemistry and double immunofluorescence labelling of frozen skin biopsies taken from normal and dcSSc patients to determine whether a phenotypic link between pericytes and myofibroblasts exists in dcSSc. Using α-smooth muscle actin, the ED-A splice variant of fibronectin (ED-A FN) and Thy-1 to identify myofibroblasts, we demonstrated the presence of myofibroblasts in fibrotic dcSSc skin. Myofibroblasts were totally absent from control skin, atrophic stage dcSSc skin and non-lesional skin. Using double immunofluorescence labelling, both myofibroblasts and pericytes were shown to express ED-A FN and Thy-1 in dcSSc skin but not in control skin. Proliferating cell nuclear antigen was also expressed by myofibroblasts and pericytes in dcSSc skin while being absent in control skin. These observations suggest that the presence of myofibroblasts may represent a transitional phase during the fibrotic stages of dcSSc and that Thy-1+ve pericytes participate in the fibrogenic development of dcSSc by synthesizing ED-A FN, which may be associated with a proliferation and transition of pericytes and fibroblasts to myofibroblasts, thus linking microvascular damage and fibrosis.
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