Niebler, Stephan and Angele, Peter and Kujat, Richard and Bosserhoff, Anja K. (2015) Hypoxia-Inducible Factor 1 Is an Inductor of Transcription Factor Activating Protein 2 Epsilon Expression during Chondrogenic Differentiation. BIOMED RESEARCH INTERNATIONAL: 380590. ISSN 2314-6133, 2314-6141
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The transcription factor AP-2 epsilon (activating enhancer-binding protein epsilon) is expressed in cartilage of humans and mice. However, knowledge about regulatory mechanisms influencing AP-2 epsilon expression is limited. Using quantitative real time PCR, we detected a significant increase in AP-2 epsilon 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 epsilon suggesting that hypoxia might represent an external regulator of AP-2 epsilon 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 epsilon, siRNA against HIF1 alpha led to a significantly reduced expression rate of AP-2 epsilon Additionally, we detected a significant upregulation of the AP-2 epsilon 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 epsilon 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FACTOR-I; CHONDROCYTE DIFFERENTIATION; ARTICULAR CHONDROCYTES; FACTOR 1-ALPHA; CARTILAGE; HIF-1-ALPHA; SOX9; AP-2-EPSILON; COLLAGEN; GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Unfallchirurgie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jul 2019 14:07 |
| Last Modified: | 29 Jul 2019 14:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6217 |
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