胎盘巨噬细胞在妊娠期糖尿病中作用的研究进展

Research progress on the role of placental macrophages in gestational diabetes mellitus

摘要

妊娠期糖尿病(GDM)是妊娠期常见的合并症之一,患病率约15%且逐年升高,对母婴危害巨大.近期研究发现,胎盘巨噬细胞(HBCs)在母胎界面数量、功能、极化、生物活性方面的改变可能均与GDM的发病密切相关.本文系统总结了胎盘HBCs对GDM发生、发展的影响,并探讨其发生作用的分子机制,以期为该领域相关研究提供最新的科学依据.

Abstract

Gestational diabetes mellitus (GDM) is one of the common complications during pregnancy, with a prevalence rate of about 15% and increasing year by year, posing significant risks to both mother and child. Recent studies have found that changes in the number, function, polarization and bioactivity of placental macrophages (HBCs) at the maternal-fetal interface may be closely related to the pathogenesis of GDM. This paper systematically reviews the impact of placental HBCs on the occurrence and progression of GDM and explores the molecular mechanisms underlying these effects, aiming to provide the latest scientific evidence for related research in this field.

关键词

胎盘 / 胎盘巨噬细胞 / Hofbauer细胞 / 妊娠期糖尿病

Key words

placenta / placental macrophage / Hofbauer cell / gestational diabetes mellitus

参考文献

[1] McElwain C J, McCarthy F P, McCarthy C M. Gestational diabetes mellitus and maternal immune dysregulation: what we know so far[J]. Int J Mol Sci, 2021, 22(8): 4261.

[2] Luccia T P B D, Pendeloski K P T, Ono E, et al. Unveiling the pathophysiology of gestational diabetes: studies on local and peripheral immune cells[J]. Scand J Immunol, 2020, 91(4): e12860.

[3] Pan X, Jin X, Wang J, et al. Placenta inflammation is closely associated with gestational diabetes mellitus[J]. Am J Transl Res, 2021, 13(5): 4068-4079.

[4] Baz B, Riveline J P, Gautier J F. Endocrinology of pregnancy: gestational diabetes mellitus: definition, aetiological and clinical aspects[J]. Eur J Endocrinol, 2016, 174(2): R43-51.

[5] Wang Z, Wang P, Wang Z, et al. MiRNA-548c-5p downregulates inflammatory response in preeclampsia via targeting PTPRO[J]. J Cell Physiol, 2019, 234(7): 11149-11155.

[6] Yu J, Zhou Y, Gui J, et al. Assessment of the number and function of macrophages in the placenta of gestational diabetes mellitus patients[J]. J Huazhong Univ Sci Technol Med Sci, 2013, 33(5): 725-729.

[7] Ning J, Zhang M, Cui D, et al. The pathologic changes of human placental macrophages in women with hyperglycemia in pregnancy[J]. Placenta, 2022, 130: 60-66.

[8] Krop J, Tian X, Van der Hoorn M L, et al. The mac is back: the role of macrophages in human healthy and complicated pregnancies[J]. Int J Mol Sci, 2023, 24(6): 5300.

[9] Huang Y, Du K L, Guo P Y, et al. IL-16 regulates macrophage polarization as a target gene of mir-145-3p[J]. Mol Immunol, 2019, 107: 1-9.

[10] Zhao Q, Wang X, Hu Q, et al. Suppression of TLR4 by miR-448 is involved in diabetic development via regulating macrophage polarization[J]. J Pharm Pharmacol, 2019, 71(5): 806-815.

[11] Loegl J, Hiden U, Nussbaumer E, et al. Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis[J]. Reproduction, 2016, 152(5): 447-455.

[12] Wang L, Zhang S, Wu H, et al. M2b macrophage polarization and its roles in diseases[J]. J Leukoc Biol, 2019, 106(2): 345-358.

[13] Schliefsteiner C, Peinhaupt M, Kopp S, et al. Human placental hofbauer cells maintain an anti-inflammatory m2 phenotype despite the presence of gestational diabetes mellitus[J]. Front Immunol, 2017, 8: 888.

[14] Yu Z, Liu J, Zhang R, et al. IL-37 and 38 signalling in gestational diabetes[J]. J Reprod Immunol, 2017, 124: 8-14.

[15] Roy S. miRNA in macrophage development and function[J]. Antioxid Redox Signal, 2016, 25(15): 795-804.

[16] Zhang Y H, He M, Wang Y, et al. Modulators of the balance between M1 and M2 macrophages during pregnancy[J]. Front Immunol, 2017, 8: 120.

[17] Svensson J, Jenmalm M C, Matussek A, et al. Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10[J]. J Immunol, 2011, 187(7): 3671-3682.

[18] Barke T L, Goldstein J A, Sundermann A C, et al. Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta[J]. Am J Reprod Immunol, 2018, 80(4): e13020.

[19] Pantham P, Aye I L, Powell T L. Inflammation in maternal obesity and gestational diabetes mellitus[J]. Placenta, 2015, 36(7): 709-715.

[20] Zhang J, Chi H, Xiao H, et al. Interleukin 6 (IL-6) and Tumor Necrosis Factor α (TNF-α) Single Nucleotide Polymorphisms (SNPs), Inflammation and metabolism in gestational diabetes mellitus in Inner Mongolia[J]. Med Sci Monit, 2017, 23: 4149-4157.

[21] Jiang X, Wang H. Macrophage subsets at the maternal-fetal interface[J]. Cell Mol Immunol, 2020, 17(8): 889-891.

[22] Zulu M, Martinez F, Gordon S, et al. The elusive role of placental macrophages: the Hofbauer cell[J]. J Innate Immun, 2019, 11(6): 447-456.

[23] Stirm L, Kovárová M, Perschbacher S, et al. BMI-independent effects of gestational diabetes on human placenta[J]. J Clin Endocrinol Metab, 2018, 103(9): 3299-3309.

[24] Mrizak I, Grissa O, Henault B, et al. Placental infiltration of inflammatory markers in gestational diabetic women[J]. Gen Physiol Biophys, 2014, 33(2): 169-176.

[25] Bari M F, Weickert M O, Sivakumar K, et al. Elevated soluble CD163 in gestational diabetes mellitus: secretion from human placenta and adipose tissue[J]. PLoS One, 2014, 9(7): e101327.

[26] Wang P, Wang H, Li C, et al. Dysregulation of microRNA-657 influences inflammatory response via targeting interleukin-37 in gestational diabetes mellitus[J]. J Cell Physiol, 2019, 234(5): 7141-7148.

[27] Sisino G, Bouckenooghe T, Aurientis S, et al. Diabetes during pregnancy influences Hofbauer cells, a subtype of placental macrophages, to acquire a pro-inflammatory phenotype[J]. Biochim Biophys Acta, 2013, 1832(12): 1959-1968.

[28] Feng J, Xing W, Xie L. Regulatory roles of MicroRNAs in diabetes[J]. Int J Mol Sci, 2016, 17(10): 1729.

[29] Wang P, Wang Z, Liu G, et al. miR-657 promotes macrophage polarization toward M1 by targeting FAM46C in gestational diabetes mellitus[J]. Mediators Inflamm, 2019, 2019: 4851214.

基金资助

国家儿童健康与疾病临床医学研究中心临床医学研究一般项目(NCRCCHD-G2022-GGP-17)

甘肃省自然科学基金(20JR10RA427)

甘肃省自然科学基金(22JR11RA177)