PUBLICATION
Biological outcome and mapping of total factor cascades in response to HIF induction during regenerative angiogenesis
- Authors
- Khatib, A.M., Lahlil, R., Hagedorn, M., Delomenie, C., Christophe, O., Denis, C., Siegfried, G.
- ID
- ZDB-PUB-160305-23
- Date
- 2016
- Source
- Oncotarget 7(11): 12102-20 (Journal)
- Registered Authors
- Keywords
- CoCl2, HIF, Pathology section, angiogenesis, functional enrichment, gene ontology, regeneration
- Datasets
- GEO:GSE58569, GEO:GSE58566, GEO:GSE58568, GEO:GSE58567
- MeSH Terms
-
- Animal Fins/blood supply*
- Animal Fins/physiology
- Animals
- Animals, Genetically Modified
- Basic Helix-Loop-Helix Transcription Factors/biosynthesis*
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Cell Differentiation/physiology
- Cell Hypoxia/physiology
- Cobalt/pharmacology
- Hypoxia-Inducible Factor 1/biosynthesis
- Neovascularization, Physiologic/physiology
- Regeneration/physiology*
- Signal Transduction
- Zebrafish
- PubMed
- 26933814 Full text @ Oncotarget
Citation
Khatib, A.M., Lahlil, R., Hagedorn, M., Delomenie, C., Christophe, O., Denis, C., Siegfried, G. (2016) Biological outcome and mapping of total factor cascades in response to HIF induction during regenerative angiogenesis. Oncotarget. 7(11):12102-20.
Abstract
Hypoxia Inducible Factor (HIF) is the main transcription factor that mediates cell response to hypoxia. Howeverthe complex factor cascades induced by HIF during regenerative angiogenesis are currently incompletely mapped and the biological outcome mediated by chronic HIF induction during vessel regeneration are not well known. Here, we investigated the biological impact of HIF induction on vascular regeneration and identified the differentially regulated genes during regeneration, HIF induction and hypoxic regeneration. The use of the fin zebrafish regeneration model revealed that exposure to HIF inducer (cobalt chloride) prevents vessel differentiation by maintaining their vascular plexuses in an immature state. The regenerated fins are easily breakable, lacking completely endochondral ossification. Gene expression arrays combined to gene functional enrichment analysis revealed that regenerative process and HIF induction shared the regulation of common genes mainly involved in DNA replication and proteasome complex. HIF induction during regeneration affected the expression of exclusive genes involved in cell differentiation and communication, consistent with the observed immature vascular plexuses of the regenerated fins during HIF induction. The use of morpholino (MO) knockdown strategy revealed that the expression of some of these genes such as tubulin and col10a1 are required for fin regeneration. Taken together, this study revealed the impact of HIF induction on regenerative angiogenesis and provided a framework to develop a gene network leading to regenerative process during HIF expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping