Here, in the hearts of mice with CKD or H9c2 cells induced by serum from CKD, we revealed that MAPKs, including the ERK1/2, JNK1/2, and P38 pathways, were significantly activated, showing the same increasing trend as cardiac CCN1, and were suppressed by the deficiency or inhibition of CCN1. Here, MAPK8 is linked to chronic kidney disease.