Dysregulation of CCN3 (NOV) expression in the epidermis of systemic sclerosis patients with pigmentary changes.

Systemic sclerosis (SSc) is a severe disease whose pathophysiology remains partly unknown, combining autoimmune, vascular, and fibrotic features. Recently, we evidenced a link between vasculopathy and pigmentary changes in SSc. CCN3 (NOV) is a matricellular protein implicated in both angiogenesis and pigmentation regulation, in particular melanocyte adhesion to the basal layer. We decided to study CCN3 expression in SSc epidermis. We show that in SSc patients with pigmentary changes compared to patients with normal pigmentation, CCN3 is specifically downregulated in situ in melanocytes and upregulated in keratinocytes. Moreover, the number of melanocytes is significantly decreased in SSc patients with a disease duration of more than 5 years compared to the other patients. Altogether, our findings could provide new insights on the mechanisms of pigmentary changes in SSc patients, as well as treatment adaptation in a personalized manner.