Fig. 6.

Signaling pathway involved in phosphate-induced myocardial hypertrophy. Phosphate-induced myocardial hypertrophy critically prompts the activation of calcineurin. Calcineurin dephosphorylates the NFAT-3 transcription factor in the cytoplasm, and the dephosphorylated NFAT-3 further interacts with the GATA-4 transcription factor in the nucleus to turn on the expression of hypertrophy response genes such as ANP and BNP that participate in the development of myocardial hypertrophy. Administration of the pharmacological agent CsA may completely block calcineurin enzymatic activity but may have no significant inhibitory effect on myocardial hypertrophy. Moreover, MEK1/2-ERK1/2 expression both increase significantly, and cellular hypertrophy is markedly attenuated by U0126, an ERK1/2 inhibitor. These results suggest that hyperphosphate induces myocardial hypertrophy through the ERK signaling pathway in H9c2 cells.