In turn, these soluble mediators were shown to activate RA human fibroblast-like synoviocytes (HFLS) (via JNK, Erk1/2 and Akt pathways) and human lung fibroblasts (HLFs) via JNK, Erk1/2, Akt, and SMAD2/3 pathways. The gene discussed is SMAD2; the disease is rheumatoid arthritis.