Overexpression of CYR61 in dSSc dermal fibroblast led to (A) decrease in cell proliferation as shown by ki67 staining; (B) increase of superoxide production which peaked at 48 hrs; (C) and (D) increased p21 mRNA and protein levels. (E) The senescence pathways that were activated by CYR61 in dSSc dermal fibroblasts included p53, p38, p21 and p16, ultimately leading to hypo-phosphorylation of Rb. In addition, the anti-fibrotic effect of CYR61 was also mediated by inactivation of the TGFβ pathway, as indicated by reduced levels of phosphorylated TGFβRII and SMAD2/3. n=number of patients. Results are expressed as mean +/− SD and p<0.05 was considered significant.