Inhibition of the TGF-β/Smads signaling pathway attenuates pulmonary fibrosis and induces anti-proliferative effect on synovial fibroblasts in rheumatoid arthritis.

Abstract

We explored whether transforming growth factor (TGF-β)/Smads signaling pathway influences rheumatoid arthritis (RA)-associated pulmonary fibrosis (PF) and proliferation of RA synovial fibroblast (RA-SF). Expression levels of TGF-β1 in RA + PF patients, RA patients and healthy controls were determined. Rat models of RA were successfully induced and assigned into groups. The mRNA, phosphorylation and protein expressions of TGF-β1, Smad2 and Smad3 were detected. The serum expressions of inflammatory factors were measured by ELISA. Tissue sections were observed using hematoxylin-eosin (HE) and Masson staining. The SF cells were separated and grouped. Cell viability and migration were determined. The highest expressions of TGF-β1 were found in RA + PF patients, followed by RA patients and then healthy controls. RA + PF rats were characterized by less activity, worse appetite, messy and less shining hair, thin sloppy stool and increased joint swelling. Compared with the normal group, the expressions of TGF-β1, Smad2, Smad3, IL-6 and TNF-α were elevated in the RA + PF group. Meanwhile, the swelling and pulmonary fibrosis of lung tissues was worse, the lung capacity and serum level of IL-10 were decreased. However, SB431542 can reverse the above results. The cell activity and cell migration ability of cells in the RA + PF + SB431542 group were inhibited compared to those in the blank group. Based on above findings, the inhibition of the TGF-β/Smads signaling pathway alleviates the pulmonary fibrosis in rats with RA and suppresses cell viability and migration of synovial fibroblasts.