SMAD3 and Timothy syndrome: Notably, the protein levels of p-Akt, p-Smad2, p-Smad3, p-mTOR and TGF-β1 were remarkably upregulated in TS rats (Figure 2(d-i) P˂0.01), and PLB treatment markedly downregulated the expression levels of these proteins in TS rats (Figure 2(d-i); P˂0.05).