CONICET | Buscador de Institutos y Recursos Humanos

StarD7 is up-regulated in choriocarcinoma JEG-3 cell line and belongs to the StARrelated lipids transfer proteins involved in intracellular transport and lipid metabolism. Objectives: To understand the molecular mechanisms that regulate StarD7 gene expression we examined the roles of glycogen synthase kinase (GSK)-3b and b-catenin in StarD7 transcription. Since the inactivation of GSK-3b promotes a diminution of glucose storage we also study whether alterations of glucose level modify StarD7 expression. Methods: Quantitative real time RT-PCR assays and transfection experiments with StarD7-Luc constructs were performed. Results: StarD7 mRNA levels were up-regulated by inhibition of GSK-3b activity by LiCl treatment, as well as, by over-expression of a constitutively active b-catenin. Both treatments caused induction of luciferase activity directed by the (-1525/+157). The StarD7 promoter revealed one potential binding site (-1013/-1006) for T-cell factors (TCFs), proteins that confer b-catenin mediated transcriptional activation. This region was critical for basal and b-catenin-induced promoter activity since its deletion markedly reduced luciferase reporter gene expression. A significantly increase in StarD7 mRNA was found in cells cultured in high glucose (25 mM) compared to cells cultured in low glucose (5.6 mM) medium, suggesting that high glycemic condition induces StarD7 expression. StarD7 transcript level correlated with b-catenin transcript level. Conclusions: Our findings suggest that StarD7 transcription is predominantly mediated by the GSK-3b pathway via Wnt-b-signalling associated to glucose and lipid metabolism. Supported by CONICET, FONCyT and SECyT-UNC.