Cell-specific and Hypoxia-dependent Regulation of Human HIF-3α: Inhibition of the Expression of HIF Target Genes in Vascular Cells

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2010 Nov 12

PMID 21069422

Citations 22

Authors

Antje Augstein

David M Poitz

Rudiger C Braun-Dullaeus

Ruth H Strasser

Alexander Schmeisser

Affiliations

Soon will be listed here.

Abstract

Hypoxia-inducible factors (HIF) are transcription factors responding to reduced oxygen levels and are of utmost importance for regulation of a widespread of cellular processes, e.g., angiogenesis. In contrast to HIF-1α/HIF-2α, the relevance of HIF-3α for the regulation of the HIF pathway in human vascular cells is largely unknown. HIF-3α mRNA increases under hypoxia in endothelial and vascular smooth muscle cells. Analysis of HIF-3α isoforms revealed a cell type-specific pattern, but only one isoform, HIF-3α2, is hypoxia-inducible. Reporter gene assays of the appropriate promoter localized a 31-bp fragment, mediating this hypoxic regulation. The contribution of HIF-1/2 and NFκB to the HIF-3α induction was verified. Functional studies focused on overexpression of HIF-3α isoforms, which decrease the hypoxia-mediated expression of VEGFA and Enolase2. These data support the notion of a hypoxia-induced inhibitory function of HIF-3α and demonstrate for the first time the existence of this negative regulation of HIF-signaling in vascular cells.

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