Fig. 6. Schematic showing the role of TG2 in cardiac fibrosis and the TG2/TGFβ1 positive feedback mechanism indicating its importance in the progression of cardiac fibrosis.

a How hemodynamic or oxidative stress and hypoxia can lead to an inflammatory response causing increased amounts of extracellular TGFβ1 leading to increased amounts of TG2 and increased numbers of myofibroblast leading to the deposition of a highly TG2 crosslinked fibrotic matrix. b The functional relationship between TG2 in the progression of fibrosis. The arrow shows how inactivation of TG2 can block this vicious cycle in fibrosis development