ArticleStem cell research & therapy2022
Retinoic acid inhibits the angiogenesis of human embryonic stem cell-derived endothelial cells by activating FBP1-mediated gluconeogenesis.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 28 citations in OpenAlex.
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- Topical Retinoids in Acne Vulgaris and Acne Scars-From Monotherapy to Combining Regimens.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The LAMB3-ITGA6 axis orchestrates epithelial repair in periodontitis via hemidesmosomal regulation and keratinization modulation.Frontiers in cell and developmental biology · 2026Article
- Glycometabolic Regulation of Angiogenesis: Mechanisms and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Lipid metabolism and microbial regulation analyses provide insights into the energy-saving strategies of hibernating snakes.Communications biology · 2025Article
- Cross-Disease Identification of FBP1 in Atherosclerosis and Calcific Aortic Valve Disease via Integrated Bioinformatics and Validation: Functional Analysis and Therapeutic Target Exploration.Journal of inflammation research · 2025Article
- Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.Signal transduction and targeted therapy · 2024Article
- Hypoxia-induced P4HA1 overexpression promotes post-ischemic angiogenesis by enhancing endothelial glycolysis through downregulating FBP1.Journal of translational medicine · 2024Article
- A Gluconeogenesis-Related Genes Model for Predicting Prognosis, Tumor Microenvironment Infiltration, and Drug Sensitivity in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Article
- A novel retinoic acid drug, EYE-502, inhibits choroidal neovascularization by targeting endothelial cells and pericytes.Scientific reports · 2023Article
- The miR-148/152 family contributes to angiogenesis of human pluripotent stem cell- derived endothelial cells by inhibiting MEOX2.Molecular therapy. Nucleic acids · 2023Article
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16 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundEndothelial cells are located in the inner lumen of blood and lymphatic vessels and exhibit the capacity to form new vessel branches from existing vessels through a process called angiogenesis. This process is energy intensive and tightly regulated. Glycolysis is the main energy source for angiogenesis. Retinoic acid (RA) is an active metabolite of vitamin A and exerts biological effects through its receptor retinoic acid receptor (RAR). In the clinic, RA is used to treat acne vulgaris and acute promyelocytic leukemia. Emerging evidence suggests that RA is involved in the formation of the vasculature; however, its effect on endothelial cell angiogenesis and metabolism is unclear.
methodsOur study was designed to clarify the abovementioned effect with human embryonic stem cell-derived endothelial cells (hESC-ECs) employed as a cell model.
resultsWe found that RA inhibits angiogenesis, as manifested by decreased proliferation, migration and sprouting activity. RNA sequencing revealed general suppression of glycometabolism in hESC-ECs in response to RA, consistent with the decreased glycolytic activity and glucose uptake. After screening glycometabolism-related genes, we found that fructose-1,6-bisphosphatase 1 (FBP1), a key rate-limiting enzyme in gluconeogenesis, was significantly upregulated after RA treatment. After silencing or pharmacological inhibition of FBP1 in hESC-ECs, the capacity for angiogenesis was enhanced, and the inhibitory effect of RA was reversed. ChIP-PCR demonstrated that FBP1 is a target gene of RAR. When hESC-ECs were treated with the RAR inhibitor BMS493, FBP1 expression was decreased and the effect of RA on angiogenesis was partially blocked.
conclusionsThe inhibitory role of RA in glycometabolism and angiogenesis is RAR/FBP1 dependent, and FBP1 may be a novel therapeutic target for pathological angiogenesis.
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