Taken together, our results demonstrated that the Cdc42-mediated MKK3/6-p38 cascade was critical for cardiac hypertrophy and cardiac fibrosis, and our data emphasized that Cdc42 is a hypertrophic and profibrotic molecule that regulates MKK3/6-p38 signaling in cardiac remodeling. The gene discussed is MAPK14; the disease is cardiac hypertrophy.