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Delphine Ciais

Hormone-regulated angiogenesis in the adrenal cortex: ACTH regulation of the expression of angiogenic factors and of the zinc finger protein Tis11b



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Published on 19 December 2003
Thesis presented December​ 19, 2003

Abstract:
Angiogenesis is the process by which new vessels grow from the pre-existing vasculature. It is controlled by a number of growth factors and VEGF (Vascular endothelial growth factor) is among the most important. In fact, involvement of VEGF is clearly identified during hormonally controlled angiogenesis in several endocrine glands, including the adrenal cortex. Indeed ACTH, the trophic hormone of the adrenal cortex induces VEGF expression in vitro.
In this study, I examined the molecular and cellular interactions between endocrine and endothelial cells which could contribute to the hormonal control of the vasculature. Here, I show that adrenocortical cells express angiopoietin and that angiopoietin 1 is under the control of ACTH. During the process of angiogenesis, angiopoietin signaling is involved in the maturation of new vessels and in the remodeling of the vasculature. These data suggest that ACTH controls the final plasticity of the vasculature through angiopoietins.
Furthermore, we show that ACTH stimulation of adrenocortical cells induced the transcription of the gene coding for Tis11b. This protein belongs to a family of zinc finger proteins involved in the control of mRNA stability through AREs motifs (AU-Rich Elements) present in their 3'UTR. Here, I show that Tis11b binds to a 75 bp AU-rich motif in VEGF mRNA 3'UTR and triggers its destabilization.
Taken together, my results indicate that ACTH, the trophic hormone of the adrenal cortex, is involved in the control of its vasculature, in one hand through its effect on ​angiopoietins expression and in the other hand by the control of VEGF mRNA stability via the induction of Tis11b expression.

Keywords:
Angiogenesis, ACTH, VEGF, endocrine cells, endothelial cells, vasculature plasticity, Tis11B, angiopoietin

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