title: Biological outcome and mapping of total factor cascades in response to HIF induction during regenerative angiogenesis.
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.
authors.affiliation: Université Bordeaux, Pessac, France.|INSERM, LAMC, UMR 1029, Pessac, France.
authors.forename: Abdel-Majid
authors.initials: AM
authors.lastname: Khatib
authors.affiliation: INSERM U 770, Kremlin-Bicêtre, France.
authors.forename: Rachid
authors.initials: R
authors.lastname: Lahlil
authors.affiliation: Université Bordeaux, Pessac, France.|INSERM, LAMC, UMR 1029, Pessac, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Hagedorn
authors.affiliation: IFR141 IPSIT, Université Paris Sud, Chatenay-Malabry, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Delomenie
authors.affiliation: INSERM U 770, Kremlin-Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Christophe
authors.affiliation: INSERM U 770, Kremlin-Bicêtre, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Denis
authors.affiliation: Université Bordeaux, Pessac, France.|INSERM, LAMC, UMR 1029, Pessac, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Siegfried
mesh_terms: D058500:Animal Fins / Q000098:blood supply* / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D003035:Cobalt / Q000494:pharmacology; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis; D018919:Neovascularization, Physiologic / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D015027:Zebrafish
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D003035:Cobalt; D051793:Hypoxia-Inducible Factor 1; C018021:cobaltous chloride
keywords: CoCl2; HIF; Pathology Section; angiogenesis; functional enrichment; gene ontology; regeneration