不同来源外泌体中微小RNA在子痫前期的研究进展

doi:10.12280/gjfckx.20211014

摘要/Abstract

摘要：

子痫前期（pre-eclampsia,PE）的发病机制至今尚未明确,而外泌体为PE发病机制的研究提供了新的方向。有研究表明外泌体在人体中广泛存在,红细胞、上皮细胞、间充质干细胞和胎盘细胞等细胞均可分泌外泌体。而这些不同来源外泌体中的微小RNA（microRNA,miRNA）被证明可以在PE的发生及预防、治疗中发挥一定的作用,例如胎盘来源外泌体中的miRNA可能与PE的发生息息相关,脐带血来源外泌体中的miRNA可能与胚胎发育有一定关系,而间充质干细胞来源外泌体中的miRNA则可能在PE的治疗中发挥重要作用。因此,探索这些miRNA及其外泌体来源对于明确PE的发病机制及靶向治疗具有重要意义。

关键词: 先兆子痫, 外泌体, 微小RNAs, 胎盘, 间充质基质细胞

Abstract:

The pathogenesis of pre-eclampsia (PE) remains unclear. However, exosomes provide a new direction for the study of the pathogenesis of PE. Studies have shown that exosomes are widespread in the human body, and cells such as red blood cells, epithelial cells, mesenchyme stem cells, and placental cells can secrete exosomes. The microRNAs (miRNAs) in exosomes from different sources have been shown to play a definite role in the occurrence and prevention of PE. For example, miRNAs in exosomes derived from the placenta may be closely related to the pathogenesis of PE, and miRNAs in cord blood-derived exosomes may have a certain relationship with embryonic development. While miRNAs in mesenchyme stem cell-derived exosomes may play an important role in the treatment of PE. These miRNAs in exosomes from diverse sources are associated with the occurrence and development of PE. Therefore, it is important to investigate the origin of these mirnas and their exosomes in order to understand the pathogenesis and target therapy of PE..

Key words: Pre-eclampsia, Exosomes, MicroRNAs, Placenta, Mesenchymal stromal cells

何豆豆, 孙晓彤, 张慧芳, 张春阳. 不同来源外泌体中微小RNA在子痫前期的研究进展[J]. 国际妇产科学杂志, 2022, 49(4): 426-429.

HE Dou-dou, SUN Xiao-tong, ZHANG Hui-fang, ZHANG Chun-yang. Research Progress of MicroRNAs in Exosomes from Different Sources in Pre-Eclampsia[J]. Journal of International Obstetrics and Gynecology, 2022, 49(4): 426-429.

参考文献 31

[1]	赵雪娅, 杨星宇, 程蔚蔚. 外泌体微小RNA与子痫前期发病机制的研究进展[J]. 中华围产医学杂志, 2018, 21(9):622-625. doi: 10.3760/cma.j.issn.1007-9408.2018.09.010. doi: 10.3760/cma.j.issn.1007-9408.2018.09.010
[2]	Hu S, Li J, Tong M, et al. MicroRNA-144-3p may participate in the pathogenesis of preeclampsia by targeting Cox-2[J]. Mol Med Rep, 2019, 19(6):4655-4662. doi: 10.3892/mmr.2019.10150. doi: 10.3892/mmr.2019.10150
[3]	Czernek L, Düchler M. Exosomes as Messengers Between Mother and Fetus in Pregnancy[J]. Int J Mol Sci, 2020, 21(12):4264. doi: 10.3390/ijms21124264. doi: 10.3390/ijms21124264
[4]	Johnstone RM, Adam M, Hammond JR, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes)[J]. J Biol Chem, 1987, 262(19):9412-9420. pmid: 3597417
[5]	Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release[J]. Cell Mol Life Sci, 2018, 75(2):193-208. doi: 10.1007/s00018-017-2595-9. doi: 10.1007/s00018-017-2595-9
[6]	Munich S, Sobo-Vujanovic A, Buchser WJ, et al. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands[J]. Oncoimmunology, 2012, 1(7):1074-1083. doi: 10.4161/onci.20897. doi: 10.4161/onci.20897
[7]	Prada I, Meldolesi J. Binding and Fusion of Extracellular Vesicles to the Plasma Membrane of Their Cell Targets[J]. Int J Mol Sci, 2016, 17(8):1296. doi: 10.3390/ijms17081296. doi: 10.3390/ijms17081296
[8]	龚榕铨, 曹恒山, 马敏. 外泌体源性miRNA在子痫前期发病机制中的研究进展[J]. 中华临床医师杂志(电子版), 2020, 14(12):1017-1022. doi: 10.3877/cma.j.issn.1674-0785.2020.12.013. doi: 10.3877/cma.j.issn.1674-0785.2020.12.013
[9]	Jin J, Menon R. Placental exosomes: A proxy to understand pregnancy complications[J]. Am J Reprod Immunol, 2018, 79(5):e12788. doi: 10.1111/aji.12788. doi: 10.1111/aji.12788
[10]	Matsubara K, Matsubara Y, Uchikura Y, et al. Pathophysiology of Preeclampsia: The Role of Exosomes[J]. Int J Mol Sci, 2021, 22(5):2572. doi: 10.3390/ijms22052572. doi: 10.3390/ijms22052572
[11]	Kluszczyńska K, Czernek L, Cypryk W, et al. Methods for the Determination of the Purity of Exosomes[J]. Curr Pharm Des, 2019, 25(42):4464-4485. doi: 10.2174/1381612825666191206162712. doi: 10.2174/1381612825666191206162712
[12]	Ge Q, Zhou Y, Lu J, et al. miRNA in plasma exosome is stable under different storage conditions[J]. Molecules, 2014, 19(2):1568-1575. doi: 10.3390/molecules19021568. doi: 10.3390/molecules19021568
[13]	Wang Y, Du X, Wang J. Transfer of miR-15a-5p by placental exosomes promotes pre-eclampsia progression by regulating PI3K/AKT signaling pathway via CDK1[J]. Mol Immunol, 2020, 128:277-286. doi: 10.1016/j.molimm.2020.10.019. doi: 10.1016/j.molimm.2020.10.019
[14]	张涛, 孟金来. 外泌体在子痫前期血管内皮损伤中的作用[J]. 现代妇产科进展, 2021, 30(4):311-313. doi: 10.13283/j.cnki.xdfckjz. 2021.04.014. doi: 10.13283/j.cnki.xdfckjz. 2021.04.014
[15]	Hromadnikova I, Kotlabova K, Dvorakova L, et al. Postpartum profiling of microRNAs involved in pathogenesis of cardiovascular/cerebrovascular diseases in women exposed to pregnancy-related complications[J]. Int J Cardiol, 2019, 291:158-167. doi: 10.1016/j.ijcard.2019.05.036. doi: S0167-5273(19)30564-9 pmid: 31151766
[16]	Pillay P, Vatish M, Duarte R, et al. Exosomal microRNA profiling in early and late onset preeclamptic pregnant women reflects pathophysiology[J]. Int J Nanomedicine, 2019, 14:5637-5657. doi: 10.2147/IJN.S208865. doi: 10.2147/IJN.S208865
[17]	Salomon C, Guanzon D, Scholz-Romero K, et al. Placental Exosomes as Early Biomarker of Preeclampsia: Potential Role of Exosomal MicroRNAs Across Gestation[J]. J Clin Endocrinol Metab, 2017, 102(9):3182-3194. doi: 10.1210/jc.2017-00672. doi: 10.1210/jc.2017-00672 pmid: 28531338
[18]	Jia L, Zhou X, Huang X, et al. Maternal and umbilical cord serum-derived exosomes enhance endothelial cell proliferation and migration[J]. FASEB J, 2018, 32(8):4534-4543. doi: 10.1096/fj.201701337RR. doi: 10.1096/fj.201701337RR
[19]	Zhao XY, Li YM, Chen S, et al. Exosomal encapsulation of miR-125a-5p inhibited trophoblast cell migration and proliferation by regulating the expression of VEGFA in preeclampsia[J]. Biochem Biophys Res Commun, 2020, 525(3):646-653. doi: 10.1016/j.bbrc.2020.02.137. doi: 10.1016/j.bbrc.2020.02.137
[20]	Devor E, Santillan D, Scroggins S, et al. Trimester-specific plasma exosome microRNA expression profiles in preeclampsia[J]. J Matern Fetal Neonatal Med, 2020, 33(18):3116-3124. doi: 10.1080/14767058. 2019.1569614. doi: 10.1080/14767058.2019.1569614 pmid: 30700172
[21]	Li H, Ouyang Y, Sadovsky E, et al. Unique microRNA Signals in Plasma Exosomes from Pregnancies Complicated by Preeclampsia[J]. Hypertension, 2020, 75(3):762-771. doi: 10.1161/HYPERTENSIO NAHA.119.14081. doi: 10.1161/HYPERTENSIO NAHA.119.14081
[22]	Zou AX, Chen B, Li QX, et al. MiR-134 inhibits infiltration of trophoblast cells in placenta of patients with preeclampsia by decreasing ITGB1 expression[J]. Eur Rev Med Pharmacol Sci, 2018, 22(8):2199-2206. doi: 10.26355/eurrev_201804_14804. doi: 10.26355/eurrev_201804_14804
[23]	Luo R, Shao X, Xu P, et al. MicroRNA-210 contributes to preeclampsia by downregulating potassium channel modulatory factor 1[J]. Hypertension, 2014, 64(4):839-845. doi: 10.1161/HYPERTENSIO NAHA.114.03530. doi: 10.1161/HYPERTENSIO NAHA.114.03530
[24]	Ishibashi O, Ohkuchi A, Ali MM, et al. Hydroxysteroid(17-β) dehydrogenase 1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placentas: a novel marker for predicting preeclampsia[J]. Hypertension, 2012, 59(2):265-273. doi: 10.1161/HYPERTENSIONAHA.111.180232. doi: 10.1161/HYPERTENSIONAHA.111.180232 pmid: 22203747
[25]	Zhang Y, Fei M, Xue G, et al. Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease[J]. J Cell Mol Med, 2012, 16(2):249-259. doi: 10.1111/j.1582-4934.2011.01291.x. doi: 10.1111/j.1582-4934.2011.01291.x pmid: 21388517
[26]	Shen L, Li Y, Li R, et al. Placenta-associated serum exosomal miR-155 derived from patients with preeclampsia inhibits eNOS expression in human umbilical vein endothelial cells[J]. Int J Mol Med, 2018, 41(3):1731-1739. doi: 10.3892/ijmm.2018.3367. doi: 10.3892/ijmm.2018.3367 pmid: 29328396
[27]	Hromadnikova I, Dvorakova L, Kotlabova K, et al. The Prediction of Gestational Hypertension, Preeclampsia and Fetal Growth Restriction via the First Trimester Screening of Plasma Exosomal C19MC microRNAs[J]. Int J Mol Sci, 2019, 20(12):2972. doi: 10.3390/ijms20122972. doi: 10.3390/ijms20122972
[28]	Riazifar M, Mohammadi MR, Pone EJ, et al. Stem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders[J]. ACS Nano, 2019, 13(6):6670-6688. doi: 10.1021/acsnano.9b01004. doi: 10.1021/acsnano.9b01004 pmid: 31117376
[29]	Huang Q, Gong M, Tan T, et al. Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomal MicroRNA-18b-3p Inhibits the Occurrence of Preeclampsia by Targeting LEP[J]. Nanoscale Res Lett, 2021, 16(1):27. doi: 10.1186/s11671-021-03475-5. doi: 10.1186/s11671-021-03475-5 pmid: 33566191
[30]	Wang D, Na Q, Song GY, et al. Human umbilical cord mesenchymal stem cell-derived exosome-mediated transfer of microRNA-133b boosts trophoblast cell proliferation, migration and invasion in preeclampsia by restricting SGK1[J]. Cell Cycle, 2020, 19(15):1869-1883. doi: 10.1080/15384101.2020.1769394. doi: 10.1080/15384101.2020.1769394 pmid: 32597300
[31]	Cui J, Chen X, Lin S, et al. MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia[J]. Stem Cell Res Ther, 2020, 11(1):231. doi: 10.1186/s13287-020-01720-9. doi: 10.1186/s13287-020-01720-9