Herein, we found that UUO or H2O2 upregulated MAPK kinase kinase (ASK1), MAPK kinases (MEK3 and MEK4), and MAPKs (JNK and p38), and these changes were accompanied by increased apoptotic cell death and dysregulation of the controlling genes, which led to renal fibrosis. This evidence concerns the gene MAP2K4 and renal fibrosis.