Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis |
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Authors: | Vineeth?S?Rajkumar Kevin?Howell Katalin?Csiszar Christopher?P?Denton Carol?M?Black Email author" target="_blank">David?J?AbrahamEmail author |
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Institution: | (1) Centre for Rheumatology & Connective Tissue Disease, Department of Medicine, Royal Free Campus, University College London, London, UK;(2) Cardiovascular Research Center, John A Burns School of Medicine, University of Hawaii, Honolulu, HI, USA; |
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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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