Figure 7.

A working model summarizing the function of Cfast in TGF-β signaling and fibrotic gene expression

Under normal physiological conditions, Cfast transcript associates with COTL1 protein, leaving excessive COTL1 protein to bind to TRAP1. Increased expression of lncRNA Cfast under stress conditions results in the association of Cfast and COTL1, releasing the COTL1 partner protein TRAP1, which in turn binds to SMAD2/SMAD4 complex to enhance the TGF-β signaling and fibrosis. Cfast knockdown allows the association between COTL1 and TRAP1, reducing the formation of the TRAP1/SMAD2/SMAD4 complex, therefore the TGF-β signaling and fibrotic gene expression.