Although previous studies have reported elevated Smad2 and Smad3 phosphorylation in diffuse SSc fibroblasts [43,44], our results indicate that limited SSc and normal skin fibroblasts have similar Smad2 and Smad3 phosphorylation levels (Figure 4C, D), which might be attributed to phenotypic differences in TGF-β pathway activation between limited SSc and diffuse SSc skin fibroblasts [45,46]. Here, SMAD3 is linked to systemic sclerosis.