自噬在子宫内膜疾病中的研究进展

doi:10.12280/gjfckx.20250766

摘要/Abstract

摘要：

自噬是一种高度保守的细胞内降解与回收过程，其核心机制是通过溶酶体系统降解细胞自身受损、衰老或多余的生物大分子和细胞器，并将降解产物重新利用以维持细胞稳态。近年研究表明，自噬水平的变化影响多种子宫内膜疾病的发生发展，包括子宫内膜异位症（endometriosis，EMs）、子宫内膜癌和宫腔粘连（intrauterine adhesions，IUA）等。自噬在EMs和子宫内膜癌的发生和发展过程中呈现双向调控特征，既可能促进疾病的发展，也可能抑制疾病的进展。在IUA的发生过程中自噬水平下调。综述自噬在这些疾病中的作用和机制，探讨其潜在的临床应用，以期为今后的研究提供新思路。

关键词: 自噬, 子宫内膜, 子宫内膜异位症, 子宫内膜肿瘤, 宫腔粘连

Abstract:

Autophagy is a highly conserved intracellular degradation and recycling process. Its core mechanism is to degrade the damaged, senescent or redundant biomacromolecules and organelles within the cell through the lysosomal system and reuse the degradation products to maintain cellular homeostasis. Recent studies have shown that changes in autophagy levels affect the occurrence and development of various endometrial diseases, including endometriosis (EMs), endometrial cancer, and intrauterine adhesions (IUA). Autophagy shows bidirectional regulatory characteristics in the occurrence and development of EMs and endometrial cancer, which may either promote or inhibit the progression of the diseases. The level of autophagy is down regulated during the development of IUA. This review summarizes the roles and mechanisms of autophagy in these diseases and explores its potential clinical applications, aiming to provide new ideas for future research.

Key words: Autophagy, Endometrium, Endometriosis, Endometrial neoplasms, Intrauterine adhesion

刘慧珊, 陈醒, 戴辉华. 自噬在子宫内膜疾病中的研究进展[J]. 国际妇产科学杂志, 2025, 52(6): 618-623.

LIU Hui-shan, CHEN Xing, DAI Hui-hua. Research Progress on Autophagy in Endometrial Diseases[J]. Journal of International Obstetrics and Gynecology, 2025, 52(6): 618-623.

参考文献 35

[1]	Kirat D, Alahwany AM, Arisha AH, et al. Role of Macroautophagy in Mammalian Male Reproductive Physiology[J]. Cells, 2023, 12(9):1322. doi: 10.3390/cells12091322.
[2]	Hama Y, Ogasawara Y, Noda NN. Autophagy and cancer: Basic mechanisms and inhibitor development[J]. Cancer Sci, 2023, 114(7):2699-2708. doi: 10.1111/cas.15803.
[3]	Lu H, Hu H, Yang Y, et al. The inhibition of reactive oxygen species (ROS) by antioxidants inhibits the release of an autophagy marker in ectopic endometrial cells[J]. Taiwan J Obstet Gynecol, 2020, 59(2):256-261. doi: 10.1016/j.tjog.2020.01.014. pmid: 32127147
[4]	Huang Y, Yan S, Dong X, et al. Deficiency of MST1 in endometriosis related peritoneal macrophages promoted the autophagy of ectopic endometrial stromal cells by IL-10[J]. Front Immunol, 2022, 13:993788. doi: 10.3389/fimmu.2022.993788.
[5]	Zhou Y, Zhao X, Zhang L, et al. Iron overload inhibits cell proliferation and promotes autophagy via PARP1/SIRT1 signaling in endometriosis and adenomyosis[J]. Toxicology, 2022, 465:153050. doi: 10.1016/j.tox.2021.153050.
[6]	Huang J, Chen X, Liu J. High mobility group box 1 promotes endometriosis under hypoxia by regulating inflammation and autophagy in vitro and in vivo[J]. Int Immunopharmacol, 2024, 127:111397. doi: 10.1016/j.intimp.2023.111397.
[7]	Chen ML, Fan L, Huang GR, et al. Knockdown of miR-150-5p reduces hypoxia-induced autophagy and epithelial-mesenchymal transition of endometriotic cells via regulating the PDCD4/NF-κB signaling pathway[J]. Cytokine, 2023, 162:156086. doi: 10.1016/j.cyto.2022.156086.
[8]	Liu H, Liang J, Wang X, et al. ALKBH5 promotes autophagy and progression by mediating m6A methylation of lncRNA UBOX5-AS1 in endometriosis[J]. Am J Physiol Cell Physiol, 2025, 328(2):C639-C656. doi: 10.1152/ajpcell.00790.2024.
[9]	Zhu S, Chen Q, Sun J, et al. The cGAS-STING pathway promotes endometriosis by up-regulating autophagy[J]. Int Immunopharmacol, 2023, 117:109644. doi: 10.1016/j.intimp.2022.109644.
[10]	Yotova I, Proestling K, Haslinger I, et al. DIRAS3 regulates autophagy in an endometriosis epithelial cell line[J]. Reprod Biomed Online, 2023, 47(4):103251. doi: 10.1016/j.rbmo.2023.06.006.
[11]	Chen Q, Zhou Y, Yu M, et al. Transcription factor EB-mediated autophagy affects cell migration and inhibits apoptosis to promote endometriosis[J]. Apoptosis, 2024, 29(5/6):757-767. doi: 10.1007/s10495-024-01939-4.
[12]	Khashchenko EP, Vysokikh MY, Marey MV, et al. Altered Glycolysis, Mitochondrial Biogenesis, Autophagy and Apoptosis in Peritoneal Endometriosis in Adolescents[J]. Int J Mol Sci, 2024, 25(8):4238. doi: 10.3390/ijms25084238.
[13]	Siracusa R, D′Amico R, Impellizzeri D, et al. Autophagy and Mitophagy Promotion in a Rat Model of Endometriosis[J]. Int J Mol Sci, 2021, 22(10):5074. doi: 10.3390/ijms22105074.
[14]	Lei ST, Lai ZZ, Hou SH, et al. Abnormal HCK/glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis[J]. Cell Prolif, 2024, 57(11):e13702. doi: 10.1111/cpr.13702.
[15]	Wang H, Liang Z, Gou Y, et al. FTO-dependent N(6)-Methyladenosine regulates the progression of endometriosis via the ATG5/PKM2 Axis[J]. Cell Signal, 2022, 98:110406. doi: 10.1016/j.cellsig.2022.110406.
[16]	He R, Liu X, Zhang J, et al. NLRC5 Inhibits Inflammation of Secretory Phase Ectopic Endometrial Stromal Cells by Up-Regulating Autophagy in Ovarian Endometriosis[J]. Front Pharmacol, 2020, 11:1281. doi: 10.3389/fphar.2020.01281. pmid: 33013364
[17]	Choi J, Jo M, Lee E, et al. Inhibition of the NLRP3 inflammasome by progesterone is attenuated by abnormal autophagy induction in endometriotic cyst stromal cells: implications for endometriosis[J]. Mol Hum Reprod, 2022, 28(4):gaac007. doi: 10.1093/molehr/gaac007.
[18]	Pei T, Luo B, Huang W, et al. Increased Expression of YAP Inhibited the Autophagy Level by Upregulating mTOR Signal in the Eutopic ESCs of Endometriosis[J]. Front Endocrinol(Lausanne), 2022, 13:813165. doi: 10.3389/fendo.2022.813165.
[19]	Yin B, Jiang H, Liu X, et al. Enriched Environment Decelerates the Development of Endometriosis in Mouse[J]. Reprod Sci, 2020, 27(7):1423-1435. doi: 10.1007/s43032-019-00117-1. pmid: 32318984
[20]	Cai J, Wang R, Chen Y, et al. LncRNA FIRRE regulated endometrial cancer radiotherapy sensitivity via the miR-199b-5p/SIRT1/BECN1 axis-mediated autophagy[J]. Genomics, 2024, 116(1):110750. doi: 10.1016/j.ygeno.2023.110750.
[21]	方秋满, 邓青春, 周小飞, 等. 肿瘤相关中性粒细胞对人子宫内膜癌细胞EMT进程及自噬的影响研究[J]. 中国免疫学杂志, 2023, 39(3):494-499. doi: 10.3969/j.issn.1000-484X.2023.03.008.
[22]	蔡鹏宇, 张斌, 吴寰宇, 等. 调控METTL3表达对子宫内膜癌细胞增殖、凋亡的影响及机制研究[J]. 中国妇产科临床杂志, 2023, 24(1):33-35. doi: 10.13390/j.issn.1672-1861.2023.01.010.
[23]	Mahdinia E, Rostami R, Rezaei A, et al. Evaluation of autophagy related ATG4B gene, protein and miR-655-3p expression levels in endometrial cancer and hyperplasia[J]. J Gynecol Oncol, 2025, 36(2):e33. doi: 10.3802/jgo.2025.36.e33.
[24]	Zhao R, Liu Y, Wang Z, et al. UBE2C-mediated Autophagy Inhibition via Ubiquitination of SIRT1 Contributes to Endometrial Cancer Progression[J]. Mol Cancer Res, 2023, 21(6):564-577. doi: 10.1158/1541-7786.MCR-22-0825.
[25]	Zhan L, Zhang J, Zhang J, et al. LC3 and NLRC5 interaction inhibits NLRC5-mediated MHC class I antigen presentation pathway in endometrial cancer[J]. Cancer Lett, 2022, 529:37-52. doi: 10.1016/j.canlet.2021.12.031.
[26]	Kim SI, Yoon JH, Hur SY. Functional profiles of Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) in primarily cultured endometrial cancer cells[J]. J Cancer, 2021, 12(20):6289-6300. doi: 10.7150/jca.60700. pmid: 34539902
[27]	Hsin IL, Wu PJ, Tang SC, et al. β-catenin inhibitor ICG-001 suppress cell cycle progression and induce autophagy in endometrial cancer cells[J]. J Cell Physiol, 2023, 238(10):2440-2450. doi: 10.1002/jcp.31103. pmid: 37682852
[28]	Xiao Y, Jin L, Deng C, et al. Inhibition of PFKFB3 induces cell death and synergistically enhances chemosensitivity in endometrial cancer[J]. Oncogene, 2021, 40(8):1409-1424. doi: 10.1038/s41388-020-01621-4. pmid: 33420377
[29]	Zhou Z, Wang H, Zhang X, et al. Defective autophagy contributes to endometrial epithelial-mesenchymal transition in intrauterine adhesions[J]. Autophagy, 2022, 18(10):2427-2442. doi: 10.1080/15548627.2022.2038994.
[30]	Wei C, Pan Y, Zhang Y, et al. Overactivated sonic hedgehog signaling aggravates intrauterine adhesion via inhibiting autophagy in endometrial stromal cells[J]. Cell Death Dis, 2020, 11(9):755. doi: 10.1038/s41419-020-02956-2. pmid: 32934215
[31]	Zhang Z, Hu J. DKK1 loss promotes endometrial fibrosis via autophagy and exosome-mediated macrophage-to-myofibroblast transition[J]. J Transl Med, 2024, 22(1):617. doi: 10.1186/s12967-024-05402-5. pmid: 38961399
[32]	Liu J, Zhu Q, Pan Y, et al. Electroacupuncture alleviates intrauterine adhesion through regulating autophagy in rats[J]. Mol Hum Reprod, 2023, 29(11):gaad037. doi: 10.1093/molehr/gaad037.
[33]	Zhao F, Wei W, Huang D, et al. Knockdown of miR-27a reduces TGFβ-induced EMT and H2O2-induced oxidative stress through regulating mitochondrial autophagy[J]. Am J Transl Res, 202, 15(10):6071-6082.
[34]	Zhou L, Dong L, Li H, et al. Mesenchymal stem cell-derived exosomes ameliorate TGF-β1-induced endometrial fibrosis by altering their miRNA profile[J]. Am J Transl Res, 2023, 15(5):3203-3216. pmid: 37303669
[35]	Mao Y, Wang M, Xiong Y, et al. MELTF Might Regulate Ferroptosis, Pyroptosis, and Autophagy in Platelet-Rich Plasma-Mediated Endometrial Epithelium Regeneration[J]. Reprod Sci, 2023, 30(5):1506-1520. doi: 10.1007/s43032-022-01101-y.