ArticleGenome biology2025
Lactate-binding protein DNMT3A in HRMECs promotes angiogenesis by upregulating VEGFA through HIF-1α lactylation.
Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- [Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Review
- Integrative Genomic and Transcriptomic Insights into High-Altitude Adaptation in Changthangi Goats.Applied biochemistry and biotechnology · 2026Article
- Protein lactylation in cancer: principles, programmes and therapeutic opportunities.Molecular cancer · 2026Review
- Lactate as a Cardiovascular Exerkine: Mechanisms, Signaling Pathways, and Clinical Implications.Biomolecules · 2026Review
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- Focus on Lactate and Lactylation Modification: The Potential Role in Ophthalmic Disease Treatment.International journal of molecular sciences · 2026Review
- Microenvironment-Responsive Nanomaterials for Colorectal Anastomotic Healing: A Signal-Threshold-Response Framework for Stage-Adaptive Repair.International journal of nanomedicine · 2026Review
- Lactylation Modification: From Basic Biological Process to Clinical Cardiovascular Diseases.Research (Washington, D.C.) · 2026Review
- Lactate-binding protein DNMT3A in HRMECs promotes angiogenesis by upregulating VEGFA through HIF-1α lactylation.Genome biology · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundOcular neovascularization is a leading cause of blindness. Hypoxia is associated with retinal angiogenesis. Hypoxia results in lactate accumulation, which typically precedes protein lactylation, and this plays a crucial role in ocular neovascularization. However, the underlying mechanism remains unclear. Here, we investigate the role of the DNA methyltransferase, DNMT3A, in regulating lactylation following hypoxia in ocular neovascularization.
resultsDNMT3A controls endothelial cell angiogenesis via regulating lactate-derived HIF-1α lactylation. During oxygen-induced retinopathy progression, we detected increased levels of DNMT3A, HIF-1α lactylation, and vascular endothelial growth factor (VEGF) in endothelial cells. Exogenous lactate administration significantly enhances vascularization, while inhibiting lactate uptake in the presence or absence of DNMT3A prevents endothelial cell angiogenesis and attenuates HIF-1α lactylation. We demonstrate that modulating DNMT3A expression alters HIF-1α lactylation levels, influencing angiogenesis in vitro and in vivo.
conclusionsDNMT3A facilitates lactate transport into the nucleus, where it promotes VEGFA upregulation through HIF-1α lactylation, thereby stimulating endothelial cell angiogenesis. Targeting the lactate-DNMT3A/HIF-1α lactylation/VEGFA pathway could provide new therapeutic strategies for treating ocular neovascularization disorders.
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