Fig. 6

Molecular mechanism of the regulation of type I interferon signature by VGLL3 in fibroblast-like synoviocytes of rheumatoid arthritis via targeting the Hippo pathway. In fibroblast-like synoviocytes of rheumatoid arthritis, VGLL3 inhibits the expression of WWTR1 which is the core protein in the hippo pathway. By downregulating WWTR1, VGLL3 enables the phosphorylation of IRF3 and drives the IRF3-induced IFN-β1 secretion. Secreted IFN-β1 subsequently promotes the type I IFN signature expression through autocrine IFN-β1 signaling. Blocking type I IFN signaling with Tofacitinib strongly represses the VGLL3-induced ISGs expressions