半乳糖凝集素-3在子宫内膜异位症发病机制中的研究进展

doi:10.12280/gjszjk.20250122

摘要/Abstract

摘要：

子宫内膜异位症（endometriosis，EMs）作为妇科的一种常见病和难治病，其发病机制尚不明确，可能涉及的机制包括慢性炎症、新生血管生成、雌激素依赖、孕激素反应减弱、上皮-间质转化和纤维化等。半乳糖凝集素-3（Galectin-3）是半乳糖凝集素家族中唯一具有嵌合体结构的成员，参与了细胞黏附、迁移、侵袭、血管生成和纤维化等生物学进程，与癌症和炎性疾病的发生密切相关。Galectin-3与EMs的相关性近年受到广泛关注，研究表明Galectin-3过表达可通过促进炎性细胞的存活、上皮-间质转化、纤维化及参与性激素调节等影响EMs的发生发展。综述Galectin-3的功能及其与EMs病理生理的相关性，以期为EMs的临床诊治提供新思路。

关键词: 子宫内膜异位症, 半乳糖凝集素3, 炎症, 上皮-间质转化, 新生血管化，病理性, 纤维化, 性腺甾类激素

Abstract:

The pathogenesis of endometriosis (EMs), as a common and difficult gynecological disease, is not very clear. The possible mechanisms include chronic inflammation, neovascularization, estrogen dependence, weakened progesterone response, epithelial-mesenchymal transition and fibrosis, etc. Galectin-3 is the only member of the Galectinin family with a chimeric structure. It participates in mutiple biological processes such as cell adhesion, migration, invasion, angiogenesis and fibrosis, which is closely related to the occurrence of cancer and inflammatory diseases. The correlation between Galectin-3 and EMs has received the extensive attention in recent years. The latest studies have shown that the overexpression of Galectin-3 can affect the occurrence and development of EMs by promoting the survival of inflammatory cells, epithelial-mesenchymal transition, fibrosis, and participating in the regulation of sex hormones. This article summarizes the functions of Galectin-3 and its correlation with the pathophysiology of EMs, with the aim of providing new ideas for the clinical diagnosis and treatment of EMs.

Key words: Endometriosis, Galectin 3, Inflammation, Epithelial-mesenchymal transition, Neovascularization, pathologic, Fibrosis, Gonadal steroid hormones

周媛, 王真真, 操孟冬, 沈雪. 半乳糖凝集素-3在子宫内膜异位症发病机制中的研究进展[J]. 国际生殖健康/计划生育杂志, 2025, 44(5): 429-433.

ZHOU Yuan, WANG Zhen-zhen, CAO Meng-dong, SHEN Xue. Research Progress on Galectin-3 in the Pathogenesis of Endometriosis[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(5): 429-433.

参考文献 37

[1]	Ni Z, Li Y, Song D, et al. Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity[J]. Cell Death Dis, 2022, 13(7):579. doi: 10.1038/s41419-022-05037-8. pmid: 35787614
[2]	彭超, 黄艳, 周应芳. 子宫内膜异位症的早期诊断和治疗[J]. 中国实用妇科与产科杂志, 2024, 40(5):485-489. doi: 10.19538/j.fk2024050102.
[3]	中国医师协会妇产科医师分会, 中华医学会妇产科学分会子宫内膜异位症协作组. 子宫内膜异位症诊治指南(第三版)[J]. 中华妇产科杂志, 2021, 56(12):812-824. doi: 10.3760/cma.j.cn112141-20211018-00603.
[4]	李密密, 戴伟. 子宫内膜异位症发病机制研究进展[J]. 临床医学进展, 2024, 14(5):1781-1789. doi: 10.12677/acm.2024.1451616.
[5]	Perez-Moreno E, Oyanadel C, de la Peña A, et al. Galectins in epithelial-mesenchymal transition: roles and mechanisms contributing to tissue repair, fibrosis and cancer metastasis[J]. Biol Res, 2024, 57(1):14. doi: 10.1186/s40659-024-00490-5. pmid: 38570874
[6]	Mariño KV, Cagnoni AJ, Croci DO, et al. Targeting galectin-driven regulatory circuits in cancer and fibrosis[J]. Nat Rev Drug Discov, 2023, 22(4):295-316. doi: 10.1038/s41573-023-00636-2.
[7]	Cerliani JP, Blidner AG, Toscano MA, et al. Translating the′Sugar Code′ into Immune and Vascular Signaling Programs[J]. Trends Biochem Sci, 2017, 42(4):255-273. doi: 10.1016/j.tibs.2016.11.003. pmid: 27986367
[8]	Bouffette S, Botez I, De Ceuninck F. Targeting galectin-3 in inflammatory and fibrotic diseases[J]. Trends Pharmacol Sci, 2023, 44(8):519-531. doi: 10.1016/j.tips.2023.06.001. pmid: 37391294
[9]	Yang H, Yin J, Ficarrotta K, et al. Aberrant expression and hormonal regulation of Galectin-3 in endometriosis women with infertility[J]. J Endocrinol Invest, 2016, 39(7):785-791. doi: 10.1007/s40618-016-0435-7. pmid: 26886939
[10]	Jarollahi S, Chaichian S, Jarollahi A, et al. The Diagnostic Accuracy of Galectin-9 for Diagnosis of Endometriosis in Comparison with Laparoscopy[J]. J Reprod Infertil, 2022, 23(4):271-278. doi: 10.18502/jri.v23i4.10812. pmid: 36452187
[11]	Wang H, Zhao Y, Ren B, et al. Endometrial regenerative cells with galectin-9 high-expression attenuate experimental autoimmune hepatitis[J]. Stem Cell Res Ther, 2021, 12(1):541. doi: 10.1186/s13287-021-02604-2. pmid: 34654474
[12]	Noël JC, Chapron C, Borghese B, et al. Galectin-3 is overexpressed in various forms of endometriosis[J]. Appl Immunohistochem Mol Morphol, 2011, 19(3):253-257. doi: 10.1097/PAI.0b013e3181f5a05e.
[13]	Butler CA, Popescu AS, Kitchener E, et al. Microglial phagocytosis of neurons in neurodegeneration, and its regulation[J]. J Neurochem, 2021, 158(3):621-639. doi: 10.1111/jnc.15327.
[14]	Slack RJ, Mills R, Mackinnon AC. The therapeutic potential of galectin-3 inhibition in fibrotic disease[J]. Int J Biochem Cell Biol, 2021,130:105881. doi: 10.1016/j.biocel.2020.105881.
[15]	Hisrich BV, Young RB, Sansone AM, et al. Role of Human Galectins in Inflammation and Cancers Associated with Endometriosis[J]. Biomolecules, 2020, 10(2):230. doi: 10.3390/biom10020230.
[16]	Mattos RM, Machado DE, Perini JA, et al. Galectin-3 plays an important role in endometriosis development and is a target to endometriosis treatment[J]. Mol Cell Endocrinol, 2019, 486:1-10. doi: 10.1016/j.mce.2019.02.007. pmid: 30753853
[17]	Dos Santos SN, Sheldon H, Pereira JX, et al. Galectin-3 acts as an angiogenic switch to induce tumor angiogenesis via Jagged-1/Notch activation[J]. Oncotarget, 2017, 8(30):49484-49501. doi: 10.18632/oncotarget.17718. pmid: 28533486
[18]	Ahmed R, Anam K, Ahmed H. Development of Galectin-3 Targeting Drugs for Therapeutic Applications in Various Diseases[J]. Int J Mol Sci, 2023, 24(9):8116. doi: 10.3390/ijms24098116.
[19]	Koninckx PR, Fernandes R, Ussia A, et al. Pathogenesis Based Diagnosis and Treatment of Endometriosis[J]. Front Endocrinol(Lausanne), 2021,12:745548. doi: 10.3389/fendo.2021.745548.
[20]	Gloushankova NA, Zhitnyak IY, Rubtsova SN. Role of Epithelial-Mesenchymal Transition in Tumor Progression[J]. Biochemistry(Mosc), 2018, 83(12):1469-1476. doi: 10.1134/S0006297918120052.
[21]	Das V, Bhattacharya S, Chikkaputtaiah C, et al. The basics of epithelial-mesenchymal transition (EMT): A study from a structure, dynamics, and functional perspective[J]. J Cell Physiol, 2019, 234(9):14535-14555. doi: 10.1002/jcp.28160.
[22]	Zubrzycka A, Migdalska-Sęk M, Jędrzejczyk S, et al. Circulating miRNAs Related to Epithelial-Mesenchymal Transitions (EMT) as the New Molecular Markers in Endometriosis[J]. Curr Issues Mol Biol, 2021, 43(2):900-916. doi: 10.3390/cimb43020064. pmid: 34449536
[23]	Lih Yuan T, Sulaiman N, Nur Azurah AG, et al. Oestrogen-induced epithelial-mesenchymal transition (EMT) in endometriosis: Aetiology of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome[J]. Front Physiol, 2022,13:937988. doi: 10.3389/fphys.2022.937988.
[24]	Marconi GD, Fonticoli L, Rajan TS, et al. Epithelial-Mesenchymal Transition (EMT): The Type-2 EMT in Wound Healing, Tissue Regeneration and Organ Fibrosis[J]. Cells, 2021, 10(7):1587. doi: 10.3390/cells10071587.
[25]	Wang T, Ou L, Li X, et al. Inhibition of Galectin-3 attenuates silica particles-induced silicosis via regulating the GSK-3β/β-catenin signal pathway-mediated epithelial-mesenchymal transition[J]. Chem Biol Interact, 2022,368:110218. doi: 10.1016/j.cbi.2022.110218.
[26]	Abobeleira JP, Neto AC, Mauersberger J, et al. Evidence of Browning and Inflammation Features in Visceral Adipose Tissue of Women with Endometriosis[J]. Arch Med Res, 2024, 55(7):103064. doi: 10.1016/j.arcmed.2024.103064.
[27]	Ruane PT, Garner T, Parsons L, et al. Trophectoderm differentiation to invasive syncytiotrophoblast is promoted by endometrial epithelial cells during human embryo implantation[J]. Hum Reprod, 2022, 37(4):777-792. doi: 10.1093/humrep/deac008.
[28]	de Mattos RM, Pereira PR, Barros EG, et al. Aberrant levels of Wnt/β-catenin pathway components in a rat model of endometriosis[J]. Histol Histopathol, 2016, 31(8):933-942. doi: 10.14670/HH-11-730. pmid: 26853489
[29]	Ganieva U, Nakamura T, Osuka S, et al. Involvement of Transcription Factor 21 in the Pathogenesis of Fibrosis in Endometriosis[J]. Am J Pathol, 2020, 190(1):145-157. doi: 10.1016/j.ajpath.2019.09.008. pmid: 31610174
[30]	Viganò P, Ottolina J, Bartiromo L, et al. Cellular Components Contributing to Fibrosis in Endometriosis: A Literature Review[J]. J Minim Invasive Gynecol, 2020, 27(2):287-295. doi: 10.1016/j.jmig.2019.11.011.
[31]	Wu Q, Sun S, Wei L, et al. Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3[J]. Cell Mol Life Sci, 2022, 79(3):137. doi: 10.1007/s00018-022-04137-0. pmid: 35182235
[32]	Yang G, Deng Y, Cao G, et al. Galectin-3 promotes fibrosis in ovarian endometriosis[J]. PeerJ, 2024,12:e16922. doi: 10.7717/peerj.16922.
[33]	Xiao F, Liu X, Guo SW. Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis[J]. Front Immunol, 2020,11:610963. doi: 10.3389/fimmu.2020.610963.
[34]	Nothnick WB. MicroRNAs and Progesterone Receptor Signaling in Endometriosis Pathophysiology[J]. Cells, 2022, 11(7):1096. doi: 10.3390/cells11071096.
[35]	Gardella B, Rispoli E, Pasquali MF, et al. Aromatase inhibitors in the pharmacotherapy of endometriosis[J]. Expert Opin Pharmacother, 2023, 24(9):1067-1073. doi: 10.1080/14656566.2023.2209315.
[36]	栾允峰, 黄桂香. Galectin-3在子宫内膜方面的研究进展[J]. 临床医药实践, 2010, 19(12):785-787.
[37]	Bojić-Trbojević Ž, Jovanović Krivokuća M, Vilotić A, et al. Human trophoblast requires galectin-3 for cell migration and invasion[J]. Sci Rep, 2019, 9(1):2136. doi: 10.1038/s41598-018-38374-w.