PDF(Pubmed)
Abstract：
Endometriosis is defined as a condition with endometrium-like tissues migrating outside of the pelvic cavity. However, the mechanism of endometriosis is still unclear. Lactate can be covalently modified to lysine residues of histones and other proteins, which is called lactylation. The results showed that the higher level of lactate and lactate dehydrogenase A enhanced the histone H3 lysine 18 lactylation (H3K18lac) in ectopic endometrial tissues and ectopic endometrial stromal cells than that in normal endometrial tissues and normal endometrial stromal cells. Lactate promoted cell proliferation, migration, and invasion in endometriosis. Mechanistically, lactate induced H3K18lac to promote the expression of high-mobility group box 1 (HMGB1) in endometriosis, and HMGB1 knockdown significantly reduced the cell proliferation, migration, and invasion of the lactate-treated cells through the phosphorylation of AKT. In conclusion, lactate could induce histone lactylation to promote endometriosis progression by upregulating the expression of HMGB1, which may provide a novel target for the prevention and treatment of endometriosis.
摘要：
子宫内膜异位症定义为子宫内膜样组织迁移到盆腔外的病症。然而,子宫内膜异位症的发病机制尚不清楚。乳酸盐可以共价修饰为组蛋白和其他蛋白质的赖氨酸残基，这就是所谓的乳酸化。结果表明，与正常子宫内膜组织和正常子宫内膜基质细胞相比，异位子宫内膜组织和异位子宫内膜基质细胞中更高水平的乳酸和乳酸脱氢酶A增强组蛋白H3赖氨酸18（H3K18lac）。乳酸促进细胞增殖，迁移,和子宫内膜异位症的侵袭。机械上,乳酸诱导的H3K18lac促进子宫内膜异位症高迁移率族蛋白1（HMGB1）的表达,和HMGB1敲低显著降低细胞增殖，迁移,和通过AKT的磷酸化侵入乳酸处理的细胞。总之,乳酸可通过上调HMGB1的表达诱导组蛋白乳酸化促进子宫内膜异位症进展,为子宫内膜异位症的防治提供新的靶点。
