子宫内膜异位症发生发展中的HIF-1α及其相关信号通路
Journal of International Reproductive Health/Family Planning(2022)
Abstract
盆腔低氧微环境是子宫内膜异位症(endometriosis,EMs)发生、发展的重要因素之一.在低氧环境中,缺氧诱导因子1α(hypoxia-inducible factor-1 alpha,HIF-1α)参与子宫内膜组织的血管生成、炎症反应以及子宫内膜细胞的增殖凋亡、迁移侵袭和上皮-间质转化等生物学过程.研究较多的,如HIF-1α/Wnt/β-catenin、HIF-1α/长链非编码RNA(long noncoding RNA,lncRNA)UBOX5-AS1、HIF-1α/LATS1/YAP1和G蛋白耦联雌激素受体(G protein coupled estrogen receptor,GPER)/HIF-1α/基质金属蛋白酶9(matrix metalloproteinase,MMP-9)通路参与子宫内膜细胞的侵袭、迁移和上皮-间质转化;HIF-1α/转化生子因子β1(transforming growth factor-beta 1,TGF-β1)/Smad、HIF-1α/EZH2/ANTXR2通路参与异位内膜细胞的黏附;磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)/HIF-1α通路、HIF-1α/双特异性磷酸酶2(dual-specificity phosphatases 2,DUSP2)/白细胞介素6(interleukin-6,IL-6)/信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)和HIF-1α/微小RNA-210(miR-210)通路促进异位内膜细胞的存活、增殖;HIF-1α/miR-20a、miR-199a/HIF-1α/血管内皮生长因子(vascular endothelial growth factor,VEGF)、HIF-1α/鸡卵清蛋白上游启动子转录因子Ⅱ(chicken ovalbumin upstream promoter transcription factorⅡ,COUP-TFⅡ)/血管生成素(angiopoietin,Ang)等通路与异位内膜组织血管生成相关.最近研究还表明,EMs具有有氧糖酵解的糖代谢特点,以及低氧介导的HIF-1α稳定表达可促进子宫内膜细胞自噬水平.综述近年来HIF-1α及其相关信号通路对EMs发生、发展过程影响的研究进展,对于进一步探究EMs的发病机制具有重要意义.
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