信号通路调控子宫内膜异位症的研究进展

doi:10.12280/gjfckx.20200508

摘要/Abstract

摘要：

子宫内膜异位症（EMs）是育龄妇女中的常见病、疑难病,发病机制错综复杂,极具侵袭性,易转移和复发,治疗效果不甚满意,而针对其发生发展机制的研究,寻找有效治疗方法是目前妇科领域研究的焦点。近年来研究发现,异位内膜细胞的上皮间质转化、黏附侵袭和血管生成过程是EMs发生发展中的重要机制,在此过程中有多条信号通路的调控,如转化生长因子β（TGF-β）/Smad、Notch、核因子κB（NF-κB）、Wnt/β连环蛋白（β-catenin）、磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/Akt/mTOR）。阐述EMs发病过程中涉及的相关信号通路研究,为临床防治EMs提供新的思路。

关键词: 子宫内膜异位症, 信号传导, Wnt信号通路, 转化生长因子β, NF-κB, 磷酸肌醇3-激酶类

Abstract:

Endometriosis (EMs) is a common and difficult disease in women of childbearing age with complex pathogenesis. It is extremely invasive, easy to metastasize and relapse, and the therapeutic effect is not satisfactory. The research on the mechanism of its occurrence and development and the search for effective treatment is the focus of gynecological research. In recent years, studies have found that the processes of epithelial-mesenchymal transition, adhesion invasion and angiogenesis of ectopic endometrial cells are important mechanisms in the occurrence and development of EMs. There are many signal pathways in this process, such as transforming growth factor β (TGF-β)/Smad, Notch, nuclear factor κB (NF-κB), Wnt/β-catenin, phosphatidyl inositol 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR). In this paper, the related signal pathways involved in the pathogenesis of EMs were described to provide a new idea for clinical prevention and treatment of EMs.

Key words: Endometriosis, Signal transduction, Wnt signaling pathway, Transforming growth factor beta, NF-kappa B, Phosphatidylinositol 3-kinases

谢韬, 曾薇薇, 陆齐天, 周华. 信号通路调控子宫内膜异位症的研究进展[J]. 国际妇产科学杂志, 2021, 48(1): 1-4.

XIE Tao, ZENG Wei-wei, LU Qi-tian, ZHOU Hua. Advances in Research on Signaling Pathways Regulation of Endometriosis[J]. Journal of International Obstetrics and Gynecology, 2021, 48(1): 1-4.

参考文献 31

[1]	Selçuk I, Bozdağ G. Recurrence of endometriosis; risk factors, mechanisms and biomarkers; review of the literature[J]. J Turk Ger Gynecol Assoc, 2013,14(2):98-103. doi: 10.5152/jtgga.2013.52385. doi: 10.5152/jtgga.2013.52385 pmid: 24592083
[2]	朱小琳, 韩亚光, 韩延华, 等. 子宫内膜异位症相关信号通路研究进展[J]. 国际妇产科学杂志, 2019,46(4):370-373,391. doi: 10.3969/j.issn.1674-1870.2019.04.002.
[3]	马雪松, 张宗峰. 上皮-间质转化在子宫内膜异位症发病机制中的作用[J]. 国际妇产科学杂志, 2020,47(1):101-105. doi: 10.3969/j.issn.1674-1870.2020.01.024.
[4]	Drabsch Y, ten Dijke P. TGF-β signalling and its role in cancer progression and metastasis[J]. Cancer Metastasis Rev, 2012,31(3/4):553-568. doi: 10.1007/s10555-012-9375-7. doi: 10.1007/s10555-012-9375-7
[5]	冯春蝶, 王福玲, 袁芳, 等. IL-17、IL-6和TGF-β在子宫内膜异位症患者组织的表达[J]. 中国免疫学杂志, 2013,29(3):243-246. doi: 10.3969/j.issn.1000-484X.2013.03.005.
[6]	Soni UK, Chadchan SB, Kumar V, et al. A high level of TGF-B1 promotes endometriosis development via cell migration, adhesiveness, colonization, and invasiveness?[J]. Biol Reprod, 2019,100(4):917-938. doi: 10.1093/biolre/ioy242. doi: 10.1093/biolre/ioy242 pmid: 30423016
[7]	Logan PC, Yango P, Tran ND. Endometrial Stromal and Epithelial Cells Exhibit Unique Aberrant Molecular Defects in Patients With Endometriosis[J]. Reprod Sci, 2018,25(1):140-159. doi: 10.1177/1933719117704905. doi: 10.1177/1933719117704905 pmid: 28490276
[8]	Guo H, Ingolia NT, Weissman JS, et al. Mammalian microRNAs predominantly act to decrease target mRNA levels[J]. Nature, 2010,466(7308):835-840. doi: 10.1038/nature09267. doi: 10.1038/nature09267 pmid: 20703300
[9]	Wang S, Zhang M, Zhang T, et al. microRNA-141 inhibits TGF-β1-induced epithelial-to-mesenchymal transition through inhibition of the TGF-β1/SMAD2 signalling pathway in endometriosis[J]. Arch Gynecol Obstet, 2020,301(3):707-714. doi: 10.1007/s00404-019-05429-w. doi: 10.1007/s00404-019-05429-w pmid: 31903498
[10]	冯婉琴, 刘敏娟, 马颖. 信号通路在子宫内膜异位症发病中的作用研究进展[J]. 山东医药, 2018,58(42):96-99. doi: 10.3969/j.issn.1002-266X.2018.42.030.
[11]	Körbel C, Gerstner MD, Menger MD, et al. Notch signaling controls sprouting angiogenesis of endometriotic lesions[J]. Angiogenesis, 2018,21(1):37-46. doi: 10.1007/s10456-017-9580-7. doi: 10.1007/s10456-017-9580-7 pmid: 28993956
[12]	Qi S, Yan L, Liu Z, et al. Melatonin inhibits 17β-estradiol-induced migration, invasion and epithelial-mesenchymal transition in normal and endometriotic endometrial epithelial cells[J]. Reprod Biol Endocrinol, 2018,16(1):62. doi: 10.1186/s12958-018-0375-5. doi: 10.1186/s12958-018-0375-5 pmid: 29935526
[13]	Luo Y, Wang D, Chen S, et al. The role of miR-34c-5p/Notch in epithelial-mesenchymal transition (EMT) in endometriosis[J]. Cell Signal, 2020,72:109666. doi: 10.1016/j.cellsig.2020.109666. doi: 10.1016/j.cellsig.2020.109666 pmid: 32353411
[14]	Zhang M, Wang S, Tang L, et al. Downregulated circular RNA hsa_circ_0067301 regulates epithelial-mesenchymal transition in endometriosis via the miR-141/Notch signaling pathway[J]. Biochem Biophys Res Commun, 2019,514(1):71-77. doi: 10.1016/j.bbrc.2019.04.109. doi: 10.1016/j.bbrc.2019.04.109 pmid: 31023528
[15]	郎景和. 关于子宫内膜异位症的再认识及其意义[J]. 中国工程科学, 2009,11(10):137-142.
[16]	赵玲娟, 冯其金, 高瑷洁, 等. Wnt/β-catenin信号通路在子宫内膜异位症中西医诊治中的研究进展[J]. 解放军医药杂志, 2019,31(7):113-116. doi: 10.3969/j.issn.2095-140X.2019.07.027.
[17]	Nanda A, Thangapandi K, Banerjee P, et al. Cytokines, Angiogenesis, and Extracellular Matrix Degradation are Augmented by Oxidative Stress in Endometriosis[J]. Ann Lab Med, 2020,40(5):390-397. doi: 10.3343/alm.2020.40.5.390. doi: 10.3343/alm.2020.40.5.390 pmid: 32311852
[18]	González-Ramos R, Rocco J, Rojas C, et al. Physiologic activation of nuclear factor kappa-B in the endometrium during the menstrual cycle is altered in endometriosis patients[J]. Fertil Steril, 2012,97(3):645-651. doi: 10.1016/j.fertnstert.2011.12.006. doi: 10.1016/j.fertnstert.2011.12.006
[19]	Kaponis A, Iwabe T, Taniguchi F, et al. The role of NF-kappaB in endometriosis[J]. Front Biosci(Schol Ed), 2012,4:1213-1234. doi: 10.2741/s327.
[20]	Zhang L, Li HH, Yuan M, et al. Exosomal miR-22-3p derived from peritoneal macrophages enhances proliferation, migration, and invasion of ectopic endometrial stromal cells through regulation of the SIRT1/NF-κB signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2020,24(2):571-580. doi: 10.26355/eurrev_202001_20033. doi: 10.26355/eurrev_202001_20033 pmid: 32016958
[21]	Yu J, Chen LH, Zhang B, et al. The modulation of endometriosis by lncRNA MALAT1 via NF-κB/iNOS[J]. Eur Rev Med Pharmacol Sci, 2019,23(10):4073-4080. doi: 10.26355/eurrev_201905_17908. doi: 10.26355/eurrev_201905_17908 pmid: 31173276
[22]	Matsuzaki S, Darcha C. In vitro effects of a small-molecule antagonist of the Tcf/β-catenin complex on endometrial and endometriotic cells of patients with endometriosis[J]. PLoS One, 2013,8(4):e61690. doi: 10.1371/journal.pone.0061690. doi: 10.1371/journal.pone.0061690 pmid: 23626717
[23]	Zhu X, Li Y, Zhou R, et al. Knockdown of E-cadherin expression of endometrial epithelial cells may activate Wnt/β-catenin pathway in vitro[J]. Arch Gynecol Obstet, 2018,297(1):117-123. doi: 10.1007/s00404-017-4560-0. doi: 10.1007/s00404-017-4560-0 pmid: 29018948
[24]	Heinosalo T, Gabriel M, Kallio L, et al. Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis[J]. Hum Reprod, 2018,33(5):817-831. doi: 10.1093/humrep/dey026. doi: 10.1093/humrep/dey026 pmid: 29462326
[25]	Zhu H, Cao XX, Liu J, et al. MicroRNA-488 inhibits endometrial glandular epithelial cell proliferation, migration, and invasion in endometriosis mice via Wnt by inhibiting FZD7[J]. J Cell Mol Med, 2019,23(4):2419-2430. doi: 10.1111/jcmm.14078. doi: 10.1111/jcmm.14078 pmid: 30729701
[26]	Mai H, Wei Y, Yin Y, et al. LINC01541 overexpression attenuates the 17β-Estradiol-induced migration and invasion capabilities of endometrial stromal cells[J]. Syst Biol Reprod Med, 2019,65(3):214-222. doi: 10.1080/19396368.2018.1549290. doi: 10.1080/19396368.2018.1549290 pmid: 30608887
[27]	马金赫, 王德莹, 陈秀慧, 等. PI3K/Akt/mTOR和MAPK信号通路与子宫内膜异位症的研究进展[J]. 现代妇产科进展, 2015,24(1):78-80. doi: 10.13283/j.cnki.xdfckjz.2015.01.023.
[28]	Liu JX, Luo MQ, Xia M, et al. Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro[J]. Mar Drugs, 2014,12(5):2790-2801. doi: 10.3390/md12052790. doi: 10.3390/md12052790 pmid: 24824025
[29]	Jana S, Chatterjee K, Ray AK, et al. Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis Promotes Angiogenesis in Endometriosis[J]. PLoS One, 2016,11(10):e0163540. doi: 10.1371/journal.pone.0163540. doi: 10.1371/journal.pone.0163540 pmid: 27695098
[30]	Cao Y, Ye Q, Zhuang M, et al. Ginsenoside Rg3 inhibits angiogenesis in a rat model of endometriosis through the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway[J]. PLoS One, 2017,12(11):e0186520. doi: 10.1371/journal.pone.0186520. doi: 10.1371/journal.pone.0186520 pmid: 29140979
[31]	Liu Y, Lu C, Fan L, et al. MiR-199a-5p Targets ZEB1 to Inhibit the Epithelial-Mesenchymal Transition of Ovarian Ectopic Endometrial Stromal Cells Via PI3K/Akt/mTOR Signal Pathway In Vitro and In Vivo[J]. Reprod Sci, 2020,27(1):110-118. doi: 10.1007/s43032-019-00016-5. doi: 10.1007/s43032-019-00016-5 pmid: 32046378