Lactate-binding protein DNMT3A in HRMECs promotes angiogenesis by upregulating VEGFA through HIF-1α lactylation
Uložené v:
| Názov: | Lactate-binding protein DNMT3A in HRMECs promotes angiogenesis by upregulating VEGFA through HIF-1α lactylation |
|---|---|
| Autori: | Xiaotang Wang, Jiaxing Huang, Wei Fan, Na Li, Hui Yang, Wenxian Yang, Wanqian Li, Ruonan Li, Jiangyi Liu, Xingran Li, Qian Zhou, Shengping Hou |
| Zdroj: | Genome Biology, Vol 26, Iss 1, Pp 1-21 (2025) |
| Informácie o vydavateľovi: | BMC, 2025. |
| Rok vydania: | 2025 |
| Zbierka: | LCC:Biology (General) LCC:Genetics |
| Predmety: | Biology (General), QH301-705.5, Genetics, QH426-470 |
| Popis: | Abstract Background Ocular 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. Results DNMT3A 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. Conclusions DNMT3A 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. |
| Druh dokumentu: | article |
| Popis súboru: | electronic resource |
| Jazyk: | English |
| ISSN: | 1474-760X |
| Relation: | https://doaj.org/toc/1474-760X |
| DOI: | 10.1186/s13059-025-03845-7 |
| Prístupová URL adresa: | https://doaj.org/article/057b29042cea4c27aafbc5f693582472 |
| Prístupové číslo: | edsdoj.057b29042cea4c27aafbc5f693582472 |
| Databáza: | Directory of Open Access Journals |
Full Text 
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstrakt: | Abstract Background Ocular 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. Results DNMT3A 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. Conclusions DNMT3A 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. |
|---|---|
| ISSN: | 1474760X |
| DOI: | 10.1186/s13059-025-03845-7 |