Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China.
State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong, China.
Reproduction. 2024 Jul 2;168(2). doi: 10.1530/REP-24-0018. Print 2024 Aug 1.
Abnormal glucose metabolism may be involved in the pathogenesis of endometriosis. The present study identifies that highly expressed H19 leads to increased aerobic glycolysis and histone lactylation levels in endometriosis.
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 are increased in endometriosis tissues. In 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 sodium lactate and 2-deoxy-d-glucose 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.
异常的葡萄糖代谢可能与子宫内膜异位症的发病机制有关。本研究表明，高度表达的 H19 导致子宫内膜异位症中有氧糖酵解和组蛋白乳酰化水平升高。
本研究组及其他研究小组之前的研究表明，在子宫内膜异位症中，H19 IncRNA 在在位和异位子宫内膜组织中的表达均增加。在这项研究中，我们使用免疫荧光、免疫组织化学和蛋白质定量来确定子宫内膜异位症组织中有氧糖酵解和组蛋白乳酰化水平升高。在人子宫内膜基质细胞中，我们发现高 H19 表达通过检查葡萄糖、乳酸和 ATP 水平以及测量参与糖酵解的酶的蛋白水平，导致异常的葡萄糖代谢。同时，免疫荧光和 Western blot 表明，H19 过表达细胞中组蛋白乳酰化增加。通过添加乳酸钠和 2-脱氧-d-葡萄糖改变有氧糖酵解和组蛋白乳酰化水平，证明有氧糖酵解和组蛋白乳酰化水平的升高导致细胞增殖和细胞迁移增强，促进子宫内膜异位症的发生。为了在体内验证这些发现，我们构建了子宫内膜异位症小鼠模型，证明了体内子宫内膜异位症组织的类似变化。在子宫内膜异位症病变中，有氧糖酵解和组蛋白乳酰化水平均升高。总之，这些数据表明，子宫内膜异位症患者 H19 的高表达水平促进了体内异常的葡萄糖代谢和组蛋白乳酰化水平的升高，增强了细胞增殖和迁移，促进了子宫内膜异位症的进展。我们的研究为 H19 表达与组蛋白乳酰化和葡萄糖代谢在子宫内膜异位症中的功能联系提供了依据，为疾病机制提供了新的见解，可能为新的治疗方法提供依据。
