葡萄糖代谢重编程在子宫内膜异位症中的研究进展

doi:10.12280/gjfckx.20230228

摘要/Abstract

摘要：

葡萄糖代谢重编程是肿瘤发生发展过程中的重要病理生理改变。近年研究发现，子宫内膜异位症（endometriosis，EMs）中存在与肿瘤类似的葡萄糖代谢重编程，即从线粒体氧化磷酸化向有氧糖酵解的转变。葡萄糖代谢重编程以葡萄糖摄取增加、乳酸产生增加以及活性氧产生减少为特征，不仅与EMs的疾病进展密切相关，还与患者卵子质量下降及子宫内膜容受性受损密切相关。综述EMs中葡萄糖代谢重编程的研究进展，为深入了解EMs的病理生理机制提供思路。

关键词: 子宫内膜异位症, 糖酵解, 瓦尔堡效应, 肿瘤学, 氧化磷酸化, 不育, 女（雌）性

Abstract:

Glucose metabolic reprogramming is an important pathophysiological alteration during tumor development. Recent studies have revealed that endometriosis (EMs) has similar reprogramming of glucose metabolism to tumor, namely the transition from mitochondrial oxidative phosphorylation to aerobic glycolysis. Glucose metabolic reprogramming, characterized by increased glucose uptake, increased lactic acid production, and decreased production of reactive oxygen species, is closely associated not only with disease progression of EMs, but also with decreased oocyte quality and impaired endometrial receptivity in patients. This review systematically reviews the research progress of glucose metabolic reprogramming in EMs, providing deeper insight into the pathophysiological mechanism of EMs.

Key words: Endometriosis, Glycolysis, Warburg effect, oncologic, Oxidative phosphorylation, Infertility, female

刘君君, 张玲, 刘义. 葡萄糖代谢重编程在子宫内膜异位症中的研究进展[J]. 国际妇产科学杂志, 2023, 50(5): 550-554.

LIU Jun-jun, ZHANG Ling, LIU Yi. Research Progress of Glucose Metabolic Reprogramming in Endometriosis[J]. Journal of International Obstetrics and Gynecology, 2023, 50(5): 550-554.

参考文献 35

[1]	Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate[J]. Cancer Cell, 2012, 21(3):297-308. doi: 10.1016/j.ccr.2012.02.014. pmid: 22439925
[2]	Young VJ, Brown JK, Maybin J, et al. Transforming growth factor-β induced Warburg-like metabolic reprogramming may underpin the development of peritoneal endometriosis[J]. J Clin Endocrinol Metab, 2014, 99(9):3450-3459. doi: 10.1210/jc.2014-1026. pmid: 24796928
[3]	Kobayashi H, Imanaka S. Understanding the molecular mechanisms of macrophage polarization and metabolic reprogramming in endometriosis: A narrative review[J]. Reprod Med Biol, 2022, 21(1):e12488. doi: 10.1002/rmb2.12488.
[4]	Bonavina G, Taylor HS. Endometriosis-associated infertility: From pathophysiology to tailored treatment[J]. Front Endocrinol(Lausanne), 2022, 13:1020827. doi: 10.3389/fendo.2022.1020827.
[5]	Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression[J]. Science, 2020, 368(6487):eaaw5473. doi: 10.1126/science.aaw5473.
[6]	Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation[J]. Science, 2009, 324(5930):1029-1033. doi: 10.1126/science.1160809. pmid: 19460998
[7]	Xia L, Oyang L, Lin J, et al. The cancer metabolic reprogramming and immune response[J]. Mol Cancer, 2021, 20(1):28. doi: 10.1186/s12943-021-01316-8. pmid: 33546704
[8]	Baik SH, Kang S, Lee W, et al. A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer′s Disease[J]. Cell Metab, 2019, 30(3):493-507.e6. doi: 10.1016/j.cmet.2019.06.005.
[9]	Srivastava RK, Sapra L, Mishra PK. Osteometabolism: Metabolic Alterations in Bone Pathologies[J]. Cells, 2022, 11(23):3943. doi: 10.3390/cells11233943.
[10]	Wei X, Hou Y, Long M, et al. Advances in energy metabolism in renal fibrosis[J]. Life Sci, 2023, 312:121033. doi: 10.1016/j.lfs.2022.121033.
[11]	Shen L, Chen W, Ding J, et al. The role of metabolic reprogramming of oxygen-induced macrophages in the dynamic changes of atherosclerotic plaques[J]. FASEB J, 2023, 37(3):e22791. doi: 10.1096/fj.202201486R.
[12]	Zhang HP, Sun YL, Wang YF, et al. Recent developments in the immunopathology of COVID-19[J]. Allergy, 2023, 78(2):369-388. doi: 10.1111/all.15593.
[13]	Qi X, Zhang Y, Ji H, et al. Knockdown of prohibitin expression promotes glucose metabolism in eutopic endometrial stromal cells from women with endometriosis[J]. Reprod Biomed Online, 2014, 29(6):761-770. doi: 10.1016/j.rbmo.2014.09.004. pmid: 25444511
[14]	McKinnon B, Bertschi D, Wotzkow C, et al. Glucose transporter expression in eutopic endometrial tissue and ectopic endometriotic lesions[J]. J Mol Endocrinol, 2014, 52(2):169-179. doi: 10.1530/JME-13-0194. pmid: 24412827
[15]	Bahrami A, Ayen E, Razi M, et al. Effects of atorvastatin and resveratrol against the experimental endometriosis; evidence for glucose and monocarboxylate transporters, neoangiogenesis[J]. Life Sci, 2021, 272:119230. doi: 10.1016/j.lfs.2021.119230.
[16]	Zhou J, Ding ZM, Hardiman PJ. Understanding the Role of Gui-Zhi-Fu-Ling-Capsules (Chinese Medicine) for Treatment of Endometriosis in the Rat Model: Using NMR Based Metabolomics[J]. Evid Based Complement Alternat Med, 2018, 2018:9864963. doi: 10.1155/2018/9864963.
[17]	Zheng J, Dai Y, Lin X, et al. Hypoxia-induced lactate dehydrogenase A protects cells from apoptosis in endometriosis[J]. Mol Med Rep, 2021, 24(3):637. doi: 10.3892/mmr.2021.12276.
[18]	Sharma D, Singh M, Rani R. Role of LDH in tumor glycolysis: Regulation of LDHA by small molecules for cancer therapeutics[J]. Semin Cancer Biol, 2022, 87:184-195. doi: 10.1016/j.semcancer.2022.11.007. pmid: 36371026
[19]	Lee HC, Lin SC, Wu MH, et al. Induction of Pyruvate Dehydrogenase Kinase 1 by Hypoxia Alters Cellular Metabolism and Inhibits Apoptosis in Endometriotic Stromal Cells[J]. Reprod Sci, 2019, 26(6):734-744. doi: 10.1177/1933719118789513.
[20]	Horne AW, Ahmad SF, Carter R, et al. Repurposing dichloroacetate for the treatment of women with endometriosis[J]. Proc Natl Acad Sci U S A, 2019, 116(51):25389-25391. doi: 10.1073/pnas.1916144116.
[21]	Kobayashi H, Kimura M, Maruyama S, et al. Revisiting estrogen-dependent signaling pathways in endometriosis: Potential targets for non-hormonal therapeutics[J]. Eur J Obstet Gynecol Reprod Biol, 2021, 258:103-110. doi: 10.1016/j.ejogrb.2020.12.044. pmid: 33421806
[22]	Atkins HM, Bharadwaj MS, O′Brien Cox A, et al. Endometrium and endometriosis tissue mitochondrial energy metabolism in a nonhuman primate model[J]. Reprod Biol Endocrinol, 2019, 17(1):70. doi: 10.1186/s12958-019-0513-8.
[23]	Yao Q, Jing G, Zhang X, et al. Cinnamic acid inhibits cell viability, invasion, and glycolysis in primary endometrial stromal cells by suppressing NF-κB-induced transcription of PKM2[J]. Biosci Rep,2021 Sep 9;BSR20211828. doi: 10.1042/BSR20211828.
[24]	Hou S, Lei S, Peng H, et al. Downregulating HK2 inhibits proliferation of endometrial stromal cells through a noncanonical pathway involving phosphorylation of signal transducer and activator of transcription 1 in endometriosis[J]. Biol Reprod, 2022, 107(2):488-499. doi: 10.1093/biolre/ioac081.
[25]	Wang Y, Xiu J, Yang T, et al. HSF1 promotes endometriosis development and glycolysis by up-regulating PFKFB3 expression[J]. Reprod Biol Endocrinol, 2021, 19(1):86. doi: 10.1186/s12958-021-00770-9.
[26]	Lu C, Qiao P, Fu R, et al. Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis[J]. Cell Death Dis, 2022, 13(9):790. doi: 10.1038/s41419-022-05241-6. pmid: 36109523
[27]	Laganà AS, Salmeri FM, Ban Frangež H, et al. Evaluation of M1 and M2 macrophages in ovarian endometriomas from women affected by endometriosis at different stages of the disease[J]. Gynecol Endocrinol, 2020, 36(5):441-444. doi: 10.1080/09513590.2019.1683821. pmid: 31663401
[28]	Gou Y, Li X, Li P, et al. Estrogen receptor β upregulates CCL2 via NF-κB signaling in endometriotic stromal cells and recruits macrophages to promote the pathogenesis of endometriosis[J]. Hum Reprod, 2019, 34(4):646-658. doi: 10.1093/humrep/dez019.
[29]	Vallvé-Juanico J, Houshdaran S, Giudice LC. The endometrial immune environment of women with endometriosis[J]. Hum Reprod Update, 2019, 25(5):564-591. doi: 10.1093/humupd/dmz018. pmid: 31424502
[30]	Johan MZ, Ingman WV, Robertson SA, et al. Macrophages infiltrating endometriosis-like lesions exhibit progressive phenotype changes in a heterologous mouse model[J]. J Reprod Immunol, 2019, 132:1-8. doi: 10.1016/j.jri.2019.01.002. pmid: 30772629
[31]	Gou Y, Wang H, Wang T, et al. Ectopic endometriotic stromal cells-derived lactate induces M2 macrophage polarization via Mettl3/Trib1/ERK/STAT3 signalling pathway in endometriosis[J]. Immunology, 2023, 168(3):389-402. doi: 10.1111/imm.13574.
[32]	Mao J, Zhang J, Cai L, et al. Elevated prohibitin 1 expression mitigates glucose metabolism defects in granulosa cells of infertile patients with endometriosis[J]. Mol Hum Reprod, 2022, 28(6):gaac018. doi: 10.1093/molehr/gaac018.
[33]	Pocate-Cheriet K, Santulli P, Kateb F, et al. The follicular fluid metabolome differs according to the endometriosis phenotype[J]. Reprod Biomed Online, 2020, 41(6):1023-1037. doi: 10.1016/j.rbmo.2020.09.002. pmid: 33046374
[34]	Ma LN, Huang XB, Muyayalo KP, et al. Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?[J]. Front Immunol, 2020, 11:279. doi: 10.3389/fimmu.2020.00279.
[35]	Su Y, Guo S, Liu C, et al. Endometrial pyruvate kinase M2 is essential for decidualization during early pregnancy[J]. J Endocrinol, 2020, 245(3):357-368. doi: 10.1530/JOE-19-0553. pmid: 32208360