SMAD7

SMAD7 is an intracellular protein that inhibits transforming growth factor beta 1 (TGF-β1) and may be overexpressed in IBD (Argollo et al., 2017; Currò et al., 2017; Nielsen et al., 2016).

TGF-β1, a cytokine produced by mucosal cells, downregulates immune responses by acting on several types of immune cells (Nielsen et al., 2016). Inhibition of TGF-β1 is thus liable to have pro-inflammatory effects.

TGF-β1 initially binds to the TGF-β receptor type II (TGF-βRII) after which TGF-β receptor type I (TGF-βRI) is recruited to the receptor complex and phosphorylation occurs (Currò et al., 2017; Nielsen et al., 2016). In subsequent interactions with other SMAD proteins, activated TGF-βRI phosphorylates SMAD2 on the SMAD2–SMAD3 complex, which then dissociates from TGF-βRI and recruits SMAD4 (Currò et al., 2017; Nielsen et al., 2016). This complex then translocates to the cell nucleus where it regulates transcription to produce other proteins including SMAD7 β1 (Currò et al., 2017; Nielsen et al., 2016).

Video 4. Animation showing the regulation of TGF-β1 via the SMAD7 pathway (Nielsen et al., 2016).

As SMAD7 can negatively regulate signalling of TGF-β1, inhibition of SMAD7 has the potential to be beneficial in IBD (Currò et al., 2017; Nielsen et al., 2016).