子宫内膜异位症发生发展中的HIF-1α及其相关信号通路

doi:10.12280/gjszjk.20220057

摘要/Abstract

摘要：

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 factor Ⅱ,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。

关键词: 子宫内膜异位症, 低氧, 缺氧诱导因子1,α亚基, 信号传导, 细胞增殖, 细胞凋亡, 新生血管化,病理学

Abstract:

The pelvic hypoxic microenvironment is an important factor of the pathogenesis and development of endometriosis (EMs), in which the induced expression of hypoxia-inducible factor-1α (HIF-1α) participates in the angiogenesis, inflammatory response, as well as the proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT) of endometrial cells. More and more studies showed that the HIF-1α/Wnt/β-catenin, HIF-1α/lncRNA UBOX5-AS1, HIF-1α/ LATS1/YAP1 and GPER/HIF-1α/MMP-9 pathway participated in the migration, invasion and EMT; HIF-1α/TGF-β1/Smad and HIF-1α/EZH2/ANTXR2 in the cell adhesion; PI3K/AKT/HIF-1α, HIF-1α/ DUSP2/IL-6/STAT3 and HIF-1α/miR-210 pathway in the cell survive and proliferation; HIF-1α/miR-20a, miR-199a/HIF-1α/VEGF and HIF-1α/COUP-TFⅡ/Ang pathway in the angiogenesis of ectopic endometrial tissue. The recent studies also showed the characteristics of aerobic glycolysis in ectopic endometrial tissue and the autophage activated by HIF-1α. In this review, we summarized the effects of HIF-1α and its related signaling pathways in the EMs for further exploring the pathogenesis of EMs.

Key words: Endometriosis, Hypoxia, Hypoxia-inducible factor 1,alpha subunit, Signal transduction, Cell proliferation, Apoptosis, Neovascularization,pathology

温萍华, 王细文, 张蔚, 刘义, 刘恒炜. 子宫内膜异位症发生发展中的HIF-1α及其相关信号通路[J]. 国际生殖健康/计划生育, 2022, 41(3): 258-264.

WEN Ping-hua, WANG Xi-wen, ZHANG Wei, LIU Yi, LIU Heng-wei. HIF-1α and Related Pathways in the Pathogenesis of Endometriosis[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(3): 258-264.

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