生长分化因子15在妊娠期疾病中的作用

doi:10.12280/gjszjk.20220004

摘要/Abstract

摘要：

妊娠期疾病是妊娠过程中母体及胎儿生理机能异常出现的一系列相关疾病,严重危害母婴健康。近年研究表明生长分化因子15（GDF15）在胎盘组织特异性高表达,对于维持妊娠、促进胎儿正常发育非常重要;其在妊娠剧吐、流产、妊娠期贫血、妊娠期糖尿病和妊娠期高血压疾病等多种妊娠期疾病中异常表达。GDF15作为多功能的细胞因子,可能通过调控胰岛素抵抗和葡萄糖耐受参与妊娠期能量代谢调节,同时通过调控巨噬细胞、树突状细胞等免疫细胞功能在妊娠期的免疫平衡调控方面发挥重要作用。综述GDF15在妊娠期疾病发生、发展中的作用。

关键词: 生长分化因子15, 流产, 贫血, 糖尿病,妊娠, 高血压,妊娠性

Abstract:

Gestational diseases are a series of diseases related to the abnormal physiological function of maternal and fetus during pregnancy, which seriously impair the health of maternity and infant. Recent studies have shown that the highly-specifical expression of growth differentiation factor 15(GDF15) in placental tissue is crucial to maintain gestation and to promote normal fetal development, and the expression of GDF15 is abnormal in the placental tissue of various gestational diseases, including hyperemesis gravidarum, abortion, pregnancy anemia, gestational diabetes and gestational hypertension, etc. GDF15 as a multifunctional cytokine could participate in the regulation of energy metabolism during pregnancy by regulating insulin resistance and glucose tolerance. GDF15 could also play an important role in the regulation of immune balance during pregnancy by regulating the functions of macrophages, dendritic cells and other immune cells. We review the roles of GDF15 in the pathogenesis and pathophysiology of gestational diseases.

Key words: Growth differentiation factor 15, Abortion, Anemia, Diabetes, gestational, Hypertension, pregnancy-induced

石紫云, 梁静, 张颖. 生长分化因子15在妊娠期疾病中的作用[J]. 国际生殖健康/计划生育, 2022, 41(4): 337-341.

SHI Zi-yun, LIANG Jing, ZHANG Ying. Roles of Growth Differentiation Factor 15 in Gestational Diseases[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(4): 337-341.

参考文献 32

[1]	Zhao H, Wei J, Sun J. Roles of TGF-β signaling pathway in tumor microenvironment and cancer therapy[J]. Int Immunopharmacol, 2020, 89(Pt B):107101. doi: 10.1016/j.intimp.2020.107101. doi: 10.1016/j.intimp.2020.107101
[2]	Gough NR, Xiang X, Mishra L. TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer[J]. Gastroenterology, 2021, 161(2):434-452.e15. doi: 10.1053/j.gastro.2021.04.064. doi: 10.1053/j.gastro.2021.04.064 URL
[3]	Rochette L, Méloux A, Zeller M, et al. Functional roles of GDF15 in modulating microenvironment to promote carcinogenesis[J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(8):165798. doi: 10.1016/j.bbadis.2020.165798. doi: 10.1016/j.bbadis.2020.165798 URL
[4]	Spanopoulou A, Gkretsi V. Growth differentiation factor 15 (GDF15) in cancer cell metastasis: from the cells to the patients[J]. Clin Exp Metastasis, 2020, 37(4):451-464. doi: 10.1007/s10585-020-10041-3. doi: 10.1007/s10585-020-10041-3 URL
[5]	Assadi A, Zahabi A, Hart RA. GDF15, an update of the physiological and pathological roles it plays: a review[J]. Pflugers Arch, 2020, 472(11):1535-1546. doi: 10.1007/s00424-020-02459-1. doi: 10.1007/s00424-020-02459-1 URL
[6]	Chang JY, Hong HJ, Kang SG, et al. The Role of Growth Differentiation Factor 15 in Energy Metabolism[J]. Diabetes Metab, 2020, 44(3):363-371. doi: 10.4093/dmj.2020.0087. doi: 10.4093/dmj.2020.0087
[7]	Breit SN, Brown DA, Tsai VW. The GDF15-GFRAL Pathway in Health and Metabolic Disease: Friend or Foe?[J]. Annu Physiol, 2021, 83:127-151. doi: 10.1146/annurev-physiol-022020-045449. doi: 10.1146/annurev-physiol-022020-045449
[8]	Eling TE, Baek SJ, Shim M, et al. NSAID activated gene (NAG-1), a modulator of tumorigenesis[J]. J Biochem Mol Biol, 2006, 39(6):649-655. doi: 10.5483/bmbrep.2006.39.6.649. doi: 10.5483/bmbrep.2006.39.6.649
[9]	Lawton LN, Bonaldo MF, Jelenc PC, et al. Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta[J]. Gene, 1997, 5203(1):17-26. doi: 10.1016/s0378-1119(97)00485-x. doi: 10.1016/s0378-1119(97)00485-x
[10]	Paralkar VM, Vail AL, Grasser WA, et al. Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family[J]. J Biol Chem, 1998, 273(22):13760-13767. doi: 10.1074/jbc.273.22.13760. doi: 10.1074/jbc.273.22.13760 pmid: 9593718
[11]	Morrish DW, Dakour J, Li H. Life and death in the placenta: new peptides and genes regulating human syncytiotrophoblast and extravillous cytotrophoblast lineage formation and renewal[J]. Curr Protein Pept Sci, 2001, 2(3):245-259. doi: 10.2174/1389203013381116. doi: 10.2174/1389203013381116 URL
[12]	Segerer SE, Rieger L, Kapp M, et al. MIC-1 (a multifunctional modulator of dendritic cell phenotype and function) is produced by decidual stromal cells and trophoblasts[J]. Hum Reprod, 2012, 27(1):200-209. doi: 10.1093/humrep/der358. doi: 10.1093/humrep/der358 URL
[13]	Moore AG, Brown DA, Fairlie WD, et al. The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women[J]. J Clin Endocrinol Metab, 2000, 85(12):4781-4788. doi: 10.1210/jcem.85.12.7007. doi: 10.1210/jcem.85.12.7007
[14]	Kaitu′u-Lino TJ, Bambang K, Onwude J, et al. Plasma MIC-1 and PAPP-a levels are decreased among women presenting to an early pregnancy assessment unit, have fetal viability confirmed but later miscarry[J]. PLoS One, 2013, 8(9):e72437. doi: 10.1371/journal.pone.0072437. doi: 10.1371/journal.pone.0072437 URL
[15]	Austin K, Wilson K, Saha S. Hyperemesis Gravidarum[J]. Nutr Clin Pract, 2019, 34(2):226-241. doi: 10.1002/ncp.10205. doi: 10.1002/ncp.10205 URL
[16]	Fejzo MS, Trovik J, Grooten IJ, et al. Nausea and vomiting of pregnancy and hyperemesis gravidarum[J]. Nat Rev Dis Primers, 2019, 5(1):62. doi: 10.1038/s41572-019-0110-3. doi: 10.1038/s41572-019-0110-3 URL
[17]	Oudman E, Wijnia JW, Oey M, et al. Wernicke′s encephalopathy in hyperemesis gravidarum: A systematic review[J]. Eur J Obstet Gynecol Reprod Biol, 2019, 236:84-93. doi: 10.1016/j.ejogrb.2019.03.006. doi: S0301-2115(19)30115-0 pmid: 30889425
[18]	Tsai VW, Zhang HP, Manandhar R, et al. GDF15 mediates adiposity resistance through actions on GFRAL neurons in the hindbrain AP/NTS[J]. Int J Obes(Lond), 2019, 43(12):2370-2380. doi: 10.1038/s41366-019-0365-5. doi: 10.1038/s41366-019-0365-5 URL
[19]	Garzon S, Cacciato PM, Certelli C, et al. Iron Deficiency Anemia in Pregnancy: Novel Approaches for an Old Problem[J]. Oman Med J, 2020, 35(5):e166. doi: 10.5001/omj.2020.108. doi: 10.5001/omj.2020.108 URL
[20]	Hawula ZJ, Wallace DF, Subramaniam VN, et al. Therapeutic Advances in Regulating the Hepcidin/Ferroportin Axis[J]. Pharmaceuticals(Basel), 2019, 12(4):170. doi: 10.3390/ph12040170. doi: 10.3390/ph12040170
[21]	Tanno T, Bhanu NV, Oneal PA, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin[J]. Nat Med, 2007, 13(9):1096-1101. doi: 10.1038/nm1629. doi: 10.1038/nm1629 URL
[22]	Finkenstedt A, Bianchi P, Theurl I, et al. Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency[J]. Br J Haematol, 2009, 144(5):789-793. doi: 10.1111/j.1365-2141.2008.07535.x. doi: 10.1111/j.1365-2141.2008.07535.x. URL
[23]	Albayrak C, Tarkun P, Birtaş Ateşoğlu E, et al. The role of hepcidin, GDF15, and mitoferrin-1 in iron metabolism of polycythemia vera and essential thrombocytosis patients[J]. Turk J Med Sci, 2019, 49(1):74-80. doi: 10.3906/sag-1803-13. doi: 10.3906/sag-1803-13 pmid: 30761871
[24]	Schernthaner-Reiter MH, Itariu BK, Krebs M, et al. GDF15 reflects beta cell function in obese patients independently of the grade of impairment of glucose metabolism[J]. Nutr Metab Cardiovasc Dis, 2019, 29(4):334-342. doi: 10.1016/j.numecd.2018.12.008. doi: S0939-4753(18)30364-8 pmid: 30718144
[25]	Shin MY, Kim JM, Kang YE, et al. Association between Growth Differentiation Factor 15 (GDF15) and Cardiovascular Risk in Patients with Newly Diagnosed Type 2 Diabetes Mellitus[J]. J Korean Med Sci, 2016, 31(9):1413-1418. doi: 10.3346/jkms.2016.31.9.1413. doi: 10.3346/jkms.2016.31.9.1413 URL
[26]	Nakayasu ES, Syed F, Tersey SA, et al. Comprehensive Proteomics Analysis of Stressed Human Islets Identifies GDF15 as a Target for Type 1 Diabetes Intervention[J]. Cell Metab, 2020, 31(2):363-374.e6. doi: 10.1016/j.cmet.2019.12.005. doi: S1550-4131(19)30670-9 pmid: 31928885
[27]	Tang M, Luo M, Lu W, et al. Serum growth differentiation factor 15 is associated with glucose metabolism in the third trimester in Chinese pregnant women[J]. Diabetes Res Clin Pract, 2019, 156:107823. doi: 10.1016/j.diabres.2019.107823. doi: 10.1016/j.diabres.2019.107823 URL
[28]	Banerjee S, Bhattacharjee R, Sur A, et al. A study of serum growth differentiation factor 15 in Indian women with and without gestational diabetes mellitus in the third trimester of pregnancy and its association with pro-inflammatory markers and glucose metabolism[J]. Diabetol Int, 2020, 12(3):254-259. doi: 10.1007/s13340-020-00478-y. doi: 10.1007/s13340-020-00478-y URL
[29]	Coll AP, Chen M, Taskar P, et al. GDF15 mediates the effects of metformin on body weight and energy balance[J]. Nature, 2020, 578(7795):444-448. doi: 10.1038/s41586-019-1911-y. doi: 10.1038/s41586-019-1911-y URL
[30]	Sugulle M, Dechend R, Herse F, et al. Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus[J]. Hypertension, 2009, 54(1):106-112. doi: 10.1161/HYPERTENSIONAHA.109.130583. doi: 10.1161/HYPERTENSIONAHA.109.130583 pmid: 19470878
[31]	Chen Q, Wang Y, Zhao M, et al. Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases[J]. Cytokine, 2016, 83:226-230. doi: 10.1016/j.cyto.2016.05.002. doi: S1043-4666(16)30084-9 pmid: 27173615
[32]	马占青, 韩琼. GSTM1、PIGF、GDF15联合对妊娠期高血压的诊断价值[J]. 国际检验医学杂志, 2019, 40(17):2163-2165.