MAP3K5 and cardiac hypertrophy: Therefore, in pathological settings, the toxic effects caused by IS could involve its entry of the target cell via OAT1/3 followed by the activation of ROS-ASK1-MAPKs (p38/ERK1/2)-NF-κB cascade, leading to increased expression of pro-hypertrophic (α-SkM-Ac and β-MHC) and pro-fibrotic genes (TGF-β1 & ctgf) and ultimately resulting in cardiac hypertrophy and fibrosis (Fig 12).