These results suggest that vasculopathy-induced hypoxia and oxidative stress might enhance ATP release in the dermis in SSc and that extracellular ATP-induced phosphorylation of p38 via P2Y<sub>2</sub> receptor might enhance IL-6 and collagen type I production in SSc fibroblasts.
These results strongly suggest the contribution of p38 MAPK signaling to the TGF-beta-mediated regulation of the human alpha2(I) collagen gene in normal dermal fibroblasts and constitutive upregulated expression of type I collagen and fibronectin in SSc fibroblasts.
To determine the possible role of p38 in abnormal collagen production by systemic sclerosis fibroblasts, p38 protein levels were compared in systemic sclerosis and healthy skin fibroblasts.