ArticleMolecular biology reports2012
GDF-15 promotes angiogenesis through modulating p53/HIF-1α signaling pathway in hypoxic human umbilical vein endothelial cells.
Article in Molecular biology reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- Circulating factors induced by time-restricted eating drive metabolic reprogramming in endothelial cells.GeroScience · 2026Article
- Malignant cell-secreted chemokines drive colorectal cancer progression through endothelial cell activation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- The Spleen Promotes Liver Sinusoidal Endothelial Cell Angiogenesis by Stimulating the TGFβ/Smad2/3 Pathway Through GDF15.Journal of gastroenterology and hepatology · 2026Article
- Elevated GDF15 in ocular fluids of patients with proliferative diabetic retinopathy.Frontiers in endocrinology · 2026Article
- Study on HIF-PHI combined with iron supplement in treatment of renal anemia in rats.BMC nephrology · 2025Article
- GDF15 promotes gallbladder cancer progression by activating the NF-κB mediated Vascular Endothelial Growth Factor A (VEGFA) expression.American journal of cancer research · 2025Article
- Molecular and Functional Significance of Growth Differentiation Factor-15: A Review on Cardiovascular-Kidney-Metabolic Biomarker.Current cardiology reviews · 2025Review
- Macrophages as a Source and Target of GDF-15.International journal of molecular sciences · 2024Review
- GDF15 as a key disease target and biomarker: linking chronic lung diseases and ageing.Molecular and cellular biochemistry · 2024Review
- Batokine in Central Nervous System Diseases.Molecular neurobiology · 2023Review
- Loss of growth differentiation factor 15 exacerbates lung injury in neonatal mice.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Growth Differentiation Factor 15 (GDF-15), a New Biomarker in Heart Failure Management.Current heart failure reports · 2023Review
- Role of the Stress- and Inflammation-Induced Cytokine GDF-15 in Cardiovascular Diseases: From Basic Research to Clinical Relevance.Reviews in cardiovascular medicine · 2023Review
- Increased plasma endostatin and GDF15 in indolent non-Hodgkin lymphoma.Upsala journal of medical sciences · 2023Article
- Macrophage inhibitory cytokine-1 in cancer: Beyond the cellular phenotype.Cancer letters · 2022Review
- Characterization of atherosclerotic plaques in blood vessels with low oxygenated blood and blood pressure (Pulmonary trunk): role of growth differentiation factor-15 (GDF-15).BMC cardiovascular disorders · 2021Article
- Emerging roles of growth differentiation factor-15 in brain disorders (Review).Experimental and therapeutic medicine · 2021Review
- GDF15 and Cardiac Cells: Current Concepts and New Insights.International journal of molecular sciences · 2021Review
- The Relationship Between Circulating Growth Differentiation Factor 15 Levels and Diabetic Retinopathy in Patients With Type 2 Diabetes.Frontiers in endocrinology · 2021Article
- Role of Growth Differentiation Factor 15 in Lung Disease and Senescence: Potential Role Across the Lifespan.Frontiers in medicine · 2020Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiogenesis is an important repair mechanism in response to ischemia/reperfusion (I/R) injury through increasing blood flow and oxygen supply. Previous studies suggested that growth differentiation factor 15 (GDF-15) was one of the most important factors responsible for promoting the angiogenesis process during cardiac ischemia. Here we tested the hypothesis that GDF-15 could promote angiogenesis via HIF-1α/VEGF dependent signaling pathway. Impaired angiogenic response was significantly improved, VEGF expression up-regulated and p53 inhibited by GDF-15 in hypoxic human umbilical vein endothelial cells (HUVECs). Expression of hypoxia-inducible factor 1-alpha (HIF-1α), an important transcriptional factor linked with angiogenesis, was significantly down-regulated post 24 h hypoxia, HIF-1α expression could be significantly up-regulated and HIF-1α nuclear translocation significantly enhanced by pretreatment with GDF-15 in hypoxic HUVECs. Knock-down HIF-1α by small interference RNA (siRNA) abolished GDF-15-mediated angiogenic effect and suppressed VEGF expression. Further experiments showed that GDF-15 activated HIF-1α signal via stabilizing p53-MDM2 complex and MDM2-mediated p53 ubiquitylation. Nutlin-3, an Hdm2 antagonist, promoted p53 nuclear translocation and attenuated GDF-15-induced activation of HIF-1α and downstream VEGF signaling in hypoxic HUVECs. Taken together, our results suggested that GDF-15 promoted angiogenesis in hypoxic HUVECs possibly through inhibiting p53 signal, which subsequently enhanced and stabolized HIF-1α expression, and up-regulated the related downstream angiogenic signaling.
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Registered trials
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.