XXXX and @entity10591 regulate expression of the @entity14190 receptor in cardiomyocytes.

@entity632 @entity14190 @entity19 @entity7006 @entity10591 @entity299 @entity36461 @entity41551 @entity14191
Experimental studies indicate significant cardioprotective effects of recombinant @entity14190 ( @entity14190 ) by binding to the @entity14191 ( @entity14191 ) and by inducing various molecular mechanisms, including activation of @entity7006 , a transcription factor that induces anti-apoptotic genes. However, specific molecular mechanisms of @entity14191 regulation in cardiomyocytes are unknown. We identified a 774 bp regulatory domain in the @entity14191 5' flanking region by reporter gene assays in @entity19 HL-1 cardiomyocytes. The binding sites for @entity41551 and Sp transcription factors both significantly contributed to @entity14191 promoter activity. DNA-binding studies (EMSA and ChIP assays) identified @entity7006 and @entity10591 as @entity14191 promoter-binding proteins in @entity36461 cardiomyocytes. Although @entity10591 alone stimulates @entity14191 only slightly, forced expression of @entity7006 significantly induced @entity14191 mRNA expression. In addition, knockdown of @entity7006 (but also of @entity10591 ) resulted in a significant decrease of @entity14191 transcript levels in HL-1 cardiomyocytes. Cumulative in vitro data suggest that function of the @entity10591 site is essential for the @entity7006 -mediated transcription. In vivo, analysis of @entity19 expressing an inducible small-hairpin RNA against @entity7006 confirmed suppression of @entity14191 expression in the heart. Treating @entity19 with high-dose @entity632 not only resulted in @entity7006 protein depletion, but also down-regulated @entity14191 , followed by up-regulation of @entity14191 transcripts when @entity7006 levels recovered. In conclusion, we identified @entity7006 as novel regulator of @entity14191 transcription in cardiomyocytes. In models of @entity299 , down-regulation of @entity7006 or @entity10591 may limit the accessibility of the @entity14191 for binding of erythropoiesis-stimulating agents (ESA). Thereby our data underline the essential role of @entity7006 in mediating cardioprotective effects.
