In contrast, expression of Smad7 was largely reduced in the synovial tissues of RA patients (Figure 1D), demonstrating that the imbalance of TGF-β/Smad signaling occurs in RA tissues and that the loss of Smad7 may promote activation of TGF-β/Smad3 signaling and RA inflammation. Here, SMAD3 is linked to rheumatoid arthritis.