Fig. 1.

Functional and structural features of the TGF-β/Smads pathway and the role of Smad7. TGF-β1 binding to its receptor II activates the TGF-β receptor type I kinase. TGF-β receptor type I then phosphorylates Smad2 and Smad3 (R-Smad). Smad2 and Smad3 are the critical mediators of TGF-β/Smads signaling in multiple diseases. Activated Smad2/3 combines with Smad4 to form a complex that is subsequently translocated into the nucleus. The resulting Smad complex incorporates different DNA-binding cofactors that confer target gene selectivity and influence the recruitment of either transcriptional coactivators or corepressors. Several hundred genes are regulated by TGF-β, including Smad7. Smad7 plays a negative regulatory role in the TGF-β/Smads signaling pathway by either inhibiting the activation of Smad2/3 activation or blocking the nuclear translocation of Smad2/3