Results using two-dimensional monolayer cultures and three-dimensional full-thickness human skin equivalents demonstrate that adiponectin potently suppressed the expression of Type I collagen and α-smooth muscle actin (α-SMA) in normal and scleroderma fibroblasts, and abrogated the stimulation of these responses elicited by TGF-β. The gene discussed is ADIPOQ; the disease is scleroderma.