ArticlePloS one2008
FGF2 translationally induced by hypoxia is involved in negative and positive feedback loops with HIF-1alpha.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 94 citations in OpenAlex.
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- Layer-specific molecular signatures of colon anastomotic healing and leakage in mice.Molecular medicine (Cambridge, Mass.) · 2025Article
- OCT4 translationally promotes AKT signaling as an RNA-binding protein in stressed pluripotent stem cells.Stem cell research & therapy · 2025Article
- Fatty Degenerative Osteonecrosis of the Jaw: Bridging Molecular Insights and Clinical Practice-A Scoping Review.International journal of molecular sciences · 2025Article
- Physiological oxygen conditions enhance the angiogenic properties of extracellular vesicles from human mesenchymal stem cells.Stem cell research & therapy · 2023Article
- Small molecule-mediated disruption of ribosome biogenesis synergizes with FGFR inhibitors to suppress glioma cell growth.Neuro-oncology · 2023Article
- SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions.Virology journal · 2023Article
- Mechanosensitive Ion Channel PIEZO1 Signaling in the Hall-Marks of Cancer: Structure and Functions.Cancers · 2022Review
- Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?International journal of molecular sciences · 2022Article
- Group 3 Pulmonary Hypertension: From Bench to Bedside.Circulation research · 2022Review
- The Inhibitory Effect of Selected DCells · 2022Article
- Tuning the intentional corona of cerium oxide nanoparticles to promote angiogenesis via fibroblast growth factor 2 signalling.Regenerative biomaterials · 2022Article
- Article
- Targeting IRES-dependent translation as a novel approach for treating Duchenne muscular dystrophy.RNA biology · 2021Review
- Endothelial FGF signaling is protective in hypoxia-induced pulmonary hypertension.The Journal of clinical investigation · 2021Article
- Hypoxia Pathway Proteins and Their Impact on the Blood Vasculature.International journal of molecular sciences · 2021Review
- (H)IF applicable: promotion of neurogenesis by induced HIF-2 signalling after ischaemia.Pflugers Archiv : European journal of physiology · 2021Article
- A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis.BMC genomics · 2021Article
- Expression Analysis ofBiology · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFibroblast growth factor 2 (FGF2) is a major angiogenic factor involved in angiogenesis and arteriogenesis, however the regulation of its expression during these processes is poorly documented. FGF2 mRNA contains an internal ribosome entry site (IRES), a translational regulator expected to allow mRNA expression during cellular stress. METHODOLOGY/PRINCIPAL
findingsIn the present study, we have developed a skin ischemia model in transgenic mice expressing a reporter transgene under the control of the FGF2 IRES. The results reveal that FGF2 is induced at the protein level during ischemia, concomitant with HIF-1alpha induction and a decrease in FGF2 mRNA. In addition, the FGF2 IRES is strongly activated under these ischemic conditions associated with hypoxia, whereas cap-dependent translation is repressed by 4E-BP hypophosphorylation. We also show that up-regulation of FGF2 protein expression in response to hypoxia correlates with the increase of FGF2 IRES activity in vitro, in human retinoblasts 911. The use of siRNAs targeting HIF or FGF2 indicates that FGF2 and HIF-1alpha reciprocally regulate their expression/accumulation, by a negative feedback loop in early hypoxia, followed by a positive feedback loop in late hypoxia. CONCLUSION/SIGNIFICANCE: FGF2 expression is up-regulated in vivo and in vitro in response to hypoxia. Strikingly, this up-regulation is not transcriptional. It seems to occur by an IRES-dependent mechanism, revealing new mechanistic aspects of the hypoxic response. In addition, our data show that FGF2 interacts with HIF-1alpha in a unique crosstalk, with distinct stages in early and late hypoxia. These data reveal the physiological importance of IRES-dependent translation during hypoxic stress and underline the complexity of the cellular response to hypoxia, suggesting a novel role of FGF2 in the regulation of HIF-1alpha during the induction of angiogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.