Also the transfection of the AT2 receptor into cultured neonatal cardiomyocytes induces hypertrophy. These results imply that in the heart Ang II activates AT2 to transmit a hypertrophic signal. This contrasts with other tissues where AT2 has been shown to elicit antigrowth and pro-apoptotic signals. A widely accepted AT2 antihypertrophic signaling mechanism is a direct G-protein independent activation by AT2 of the protein tyrosine phosphatase SHP-1 that blocks growth factor signals. In search of the molecular mechanism which may provide material support for the unique cardiac hypertrophic response to the AT2 receptor action in vivo, we examined the hypothesis that a specific AT2-binding or modulating protein exists in the heart. PLZF is a transcription factor which contains 9 zinc fingers in the carboxyl terminal area and its amino terminus BTB/POZ domain mediates most biological functions of the zinc finger protein. As an important transcription factor in cell differentiation and development, PLZF exhibits proapoptotic function in limb development and an antiapoptotic role in developing testis. PLZF regulates cyclin A2, c-myc, kit gene expression and is involved in the signal of AT2 and renin receptors. The function of PLZF in different tissues and cells Ginsenoside-F5 depends on its specific gene sequence context and different functional interaction partners. Several cardiac transcription factors involved in fetal heart development have been identified including GATA4,5,6, NFAT 3, Nkx 2.5 and the transcription factor regulator HDACs. A reversion of these fetal gene expressions leads to maladaptive heart function. Given that PLZF is an AT2 receptor binding protein in the heart; we hypothesized that it can interact with some of these transcription factors, specifically GATA4 in the heart. In the present study, we employed PLZF-/mice to consolidate the hypothesis that the cardiac hypertrophic action of AT2 is regulated by PLZF in vivo. In the present study, we report evidence indicating PLZF, a Kruppel-like zinc finger protein highly expressed in the heart, is a crucial transcription factor that regulates cardiac hypertrophy through the AT2 receptor in response to Ang II. Ang II-activated AT2 receptor has been shown to bind PLZF and facilitate its nuclear translocation. The present study shows that it upregulates the expression of GATA4, a key cardiac morphogenic, hypertrophy and remodeling regulator. PLZF was first recognized to fuse with retinoic acid receptor RARa in acute promyelocytic leukemia. PLZF suppresses gene transcription by recruiting corepressors to the gene regulation region and activate gene transcription with different molecular mechanism which has not been well defined. PLZF is increasingly recognized as a key regulator in cell differentiation, growth or self-renewal process. Using PLZF knockout mice, we found suppressed cardiac hypertrophy and fibrosis in PLZF-/- mice subjected to chronic Ang II stimulation. Further experiments revealed PLZF regulated GATA4 expression, a vital factor in heart development and differentiation and remodeling. GATA4 directly stimulates numerous cardiac-specific genes, including those of aand b-myosin heavy chain genes which are key indices of cardiomyocyte hypertrophy. Therefore, we believe that the expression of GATA4 directly regulated by PLZF is another important factor of the cardiac remodeling Anemarsaponin-E controlled by the transcription factor PLZF in the Ang II AT2 signaling pathway.