Thus, the results of our study provides evidence that cAMP has anti-fibrotic effects in vitro and in vivo, and that these effects depend on PKA/p-CREB signaling by disturbing p-Smad2/3 binding with CBP, and inhibiting myofibroblast differentiation in a model of silicosis (Fig. 8). This evidence concerns the gene SMAD2 and silicosis.