Systemic sclerosis (SSc) is a rare and severe connective
tissue disease combining auto-immune and vasculopathy features, ultimately leading to organ fibrosis. Impaired angiogenesis is an often silent and lifethreatening complication of the disease. Recent data point to an association between vascular involvement in SSc and skin pigmentation. CCN3 (NOV), a member of the CCN family of extra-cellular matrix proteins, is a proangiogenic factor and contributes to epidermal homeostasis. We performed skin biopsies on 26 SSc patients, both in fibrotic and non-fibrotic areas for 17 patients, and collected 18 healthy control skin specimens for
immunohistochemistry and cell culture. CCN3 expression is systematically
decreased in the skin of SSc patients compared to healthy controls,
particularly in dermal vessels. Moreover, CCN3 is decreased in vitro in
endothelial cells from SSc patients. We show that CCN3 is essential for
normal endothelial cell migration and for angiogenesis in vitro. In the
epidermis, CCN3 is specifically decreased in the melanocytes of SSc patients
with pigmentary disorders.CCN3 represents a promising therapeutic target
for SSc patients presenting with vascular involvement, which could be
detected early by the presence of skin pigmentary changes.

Decreased CCN3 expression in Systemic Sclerosis skin contributes to vasculopathy and links to pigmentary disorders