子宫内膜异位症
厌氧糖酵解
糖酵解
间质细胞
组蛋白
组蛋白H3
生物
癌症研究
化学
内分泌学
内科学
新陈代谢
生物化学
医学
基因
作者
Xin Wen,Jingyang Zhang,Zhen Xu,Muzi Li,Xiaotong Dong,Yanbo Du,Zhen Xu,Lei Yan
摘要
Previous studies from our group and others have shown increased IncRNA H19 expression in both the eutopic endometrium and the ectopic endometriosis tissue during endometriosis. In this study, we use immunofluorescence, immunohistochemistry and protein quantification to determine that levels of aerobic glycolysis and histone lactylation; which we show are increased in endometriosis tissues. In HESC cells (Human Endometrial Stromal Cells), we found that high H19 expression resulted in abnormal glucose metabolism by examining the levels of glucose, lactate, and ATP and measuring protein levels of enzymes that participate in glycolysis. At the same time, immunofluorescence and western blotting demonstrated increased histone lactylation in H19 overexpressing cells. Altering aerobic glycolysis and histone lactylation levels through the addition of Nala (sodium lactate) and 2-DG demonstrated that increased aerobic glycolysis and histone lactylation levels resulted in enhanced cell proliferation and cell migration, contributing to endometriosis. To validate these findings in vivo, we constructed an endometriosis mouse model, demonstrating similar changes in endometriosis tissues in vivo. Both aerobic glycolysis and histone lactylation levels were elevated in endometriotic lesions. Taken together, these data demonstrate elevated expression levels of H19 in endometriosis patients promote abnormal glucose metabolism and elevated histone lactylation levels in vivo, enhancing cell proliferation and migration and promoting the progression of endometriosis. Our study provides a functional link between H19 expression and histone lactylation and glucose metabolism in endometriosis, providing new insights into disease mechanisms that could result in novel therapeutic approaches.
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