In:
BioMed Research International, Hindawi Limited, Vol. 2015 ( 2015), p. 1-15
Abstract:
The transcription factor AP-2 ε (activating enhancer-binding protein epsilon) is expressed in cartilage of humans and mice. However, knowledge about regulatory mechanisms influencing AP-2 ε expression is limited. Using quantitative real time PCR, we detected a significant increase in AP-2 ε mRNA expression comparing initial and late stages of chondrogenic differentiation processes in vitro and in vivo . Interestingly, in these samples the expression pattern of the prominent hypoxia marker gene angiopoietin-like 4 (Angptl4) strongly correlated with that of AP-2 ε suggesting that hypoxia might represent an external regulator of AP-2 ε expression in mammals. In order to show this, experiments directly targeting the activity of hypoxia-inducible factor-1 (HIF1), the complex mediating responses to oxygen deprivation, were performed. While the HIF1-activating compounds 2,2′-dipyridyl and desferrioxamine resulted in significantly enhanced mRNA concentration of AP-2 ε , siRNA against HIF1 α led to a significantly reduced expression rate of AP-2 ε . Additionally, we detected a significant upregulation of the AP-2 ε mRNA level after oxygen deprivation. In sum, these different experimental approaches revealed a novel role for the HIF1 complex in the regulation of the AP-2 ε gene in cartilaginous cells and underlined the important role of hypoxia as an important external regulatory stimulus during chondrogenic differentiation modulating the expression of downstream transcription factors.
Type of Medium:
Online Resource
ISSN:
2314-6133
,
2314-6141
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2015
detail.hit.zdb_id:
2698540-8
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