Over three decades, several studies have demonstrated the upregulation of disease-associated molecules in the epidermis of SSc-involved skin, such as endothelin-1, TGF-β, CCL2, vascular endothelial growth factor, IL-21 receptor, wound healing-associated cytokeratins (keratin 6 and keratin 16), IL-1α, CTGF, IL-6, TNF-α, CCL5, psoriasin and galectin-7 [112,113,114,115,116,117,118,119,120,121]. Here, CCN2 is linked to systemic sclerosis.