Evidence has shown that the increase of ROS could activate profibrotic factors, including TGF-β through P38-MAPK, which could promote the synthesis of type IV collagen (the main component of extracellular matrix (ECM)) and fibrin connection protein, thus causing an increase in ECM, and forming early DKD (Sakai et al., 2005). The gene discussed is MAPK14; the disease is diabetic kidney disease.