SMAD7 and colitis: This seemingly paradoxical increase in the anti-inflammatory TGF-β in DSS-induced colitis may be due to overexpression of SMAD7, which negatively regulated TGF-β signaling by competing for SMAD3’s binding site on the TGF-β receptor, thereby blocking SMAD3 activation (Feagins, 2010; Alliger et al., 2020).