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 (
compared to cells cultured in low glucose (
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.
