SLRPs在胎盘发育及妊娠相关疾病中的研究进展

doi:10.12280/gjfckx.20240589

摘要/Abstract

摘要：

小富亮氨酸蛋白聚糖家族（small leucine-rich proteoglycans，SLRPs）是一类富含亮氨酸重复序列的小分子蛋白聚糖，是细胞外基质的关键组成部分，参与调控多项生理功能。SLRPs共分为5类，其中Ⅰ类SLRPs的主要成员decorin、biglycan和Ⅱ类SLRPs的主要成员lumican、fibromodulin在胎盘和子宫中的表达尤为显著，在妊娠过程中起到重要作用。这些蛋白聚糖参与维持妊娠期细胞外基质的稳态平衡，通过介导细胞间信号转导，调节绒毛外滋养层细胞的增殖、迁移和侵袭能力，影响胎盘血管的形成与功能，在维持胎盘和胎膜结构-功能完整性方面发挥重要作用，它们的异常表达或功能改变可能与子痫前期、胎儿生长受限等多种妊娠相关疾病的发病密切相关。综述SLRPs在胎盘发育和妊娠相关疾病中的作用机制，以期为临床防治提供相关理论支持。

关键词: 细胞外基质, 胎盘形成, 先兆子痫, 胎儿生长迟缓, 小富亮氨酸蛋白聚糖家族, 绒毛外滋养层细胞

Abstract:

The small leucine-rich proteoglycans (SLRPs) are a family of small proteoglycans rich in leucine repeat sequences and are key components of the extracellular matrix, involved in regulating various physiological functions. SLRPs are classified into five categories, with the main members of class Ⅰ SLRPs, such as decorin and biglycan, and the main members of class Ⅱ SLRPs, such as lumican and fibromodulin, being particularly prominent in the placenta and uterus, playing significant role during pregnancy. These proteoglycans participate in maintaining the homeostatic balance of the extracellular matrix during pregnancy, mediate intercellular signal transduction, regulate the proliferation, migration and invasion capabilities of extravillous trophoblast cells, and influence the formation and function of placental blood vessels. They play a crucial role in maintaining the structural and functional integrity of the placenta and fetal membranes. Their abnormal expression or functional alterations may be closely related to the pathogenesis of various pregnancy-related diseases, such as preeclampsia and fetal growth restriction. This review discusses the mechanisms by which SLRPs influence placental development and pregnancy-related diseases, aiming to provide theoretical support for clinical prevention and treatment.

Key words: Extracellular matrix, Placentation, Pre-eclampsia, Fetal growth retardation, Small leucine-rich proteoglycans, Extravillous trophoblast cell

张琦, 王新, 任毅, 刘超, 高慧婕. SLRPs在胎盘发育及妊娠相关疾病中的研究进展[J]. 国际妇产科学杂志, 2024, 51(5): 525-530.

ZHANG Qi, WANG Xin, REN Yi, LIU Chao, GAO Hui-jie. Research Progress on SLRPs in Placental Development and Pregnancy-Related Diseases[J]. Journal of International Obstetrics and Gynecology, 2024, 51(5): 525-530.

参考文献 40

[1]	Greenbaum S, Averbukh I, Soon E, et al. A spatially resolved timeline of the human maternal-fetal interface[J]. Nature, 2023, 619(7970):595-605. doi: 10.1038/s41586-023-06298-9.
[2]	Berdiaki A, Giatagana EM, Tzanakakis G, et al. The Landscape of Small Leucine-Rich Proteoglycan Impact on Cancer Pathogenesis with a Focus on Biglycan and Lumican[J]. Cancers(Basel), 2023, 15(14):3549. doi: 10.3390/cancers15143549.
[3]	Low S, Connor TB, Kassem IS, et al. Small Leucine-Rich Proteoglycans (SLRPs) in the Retina[J]. Int J Mol Sci, 2021, 22(14):7293. doi: 10.3390/ijms22147293.
[4]	Colon-Caraballo M, Lee N, Nallasamy S, et al. Novel regulatory roles of small leucine-rich proteoglycans in remodeling of the uterine cervix in pregnancy[J]. Matrix Biol, 2022, 105:53-71. doi: 10.1016/j.matbio.2021.11.004.
[5]	Halari CD, Zheng M, Lala PK. Roles of Two Small Leucine-Rich Proteoglycans Decorin and Biglycan in Pregnancy and Pregnancy-Associated Diseases[J]. Int J Mol Sci, 2021, 22(19):10584. doi: 10.3390/ijms221910584.
[6]	Halari CD, Renaud SJ, Lala PK. Molecular mechanisms in IL-1β-mediated decorin production by decidual cells[J]. Mol Hum Reprod, 2021, 27(12):gaab068. doi: 10.1093/molehr/gaab068.
[7]	Halari CD, Nandi P, Sidhu J, et al. Decorin-induced, preeclampsia-associated microRNA-512-3p restrains extravillous trophoblast functions by targeting USF2/PPP3R1 axis[J]. Front Cell Dev Biol, 2022,10:1014672. doi: 10.3389/fcell.2022.1014672.
[8]	Lee N, Shi L, Colon Caraballo M, et al. Mechanical Response of Mouse Cervices Lacking Decorin and Biglycan During Pregnancy[J]. J Biomech Eng, 2022, 144(6):061009. doi: 10.1115/1.4054199.
[9]	Deng J, Zhao HJ, Zhong Y, et al. H3K27me3-modulated Hofbauer cell BMP2 signalling enhancement compensates for shallow trophoblast invasion in preeclampsia[J]. EBioMedicine, 2023,93:104664. doi: 10.1016/j.ebiom.2023.104664.
[10]	Schuermans A, Truong B, Ardissino M, et al. Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia[J]. JAMA Cardiol, 2024, 9(3):209-220. doi: 10.1001/jamacardio.2023.4994.
[11]	Halari CD, Nandi P, Jeyarajah MJ, et al. Decorin production by the human decidua: role in decidual cell maturation[J]. Mol Hum Reprod, 2020, 26(10):784-796. doi: 10.1093/molehr/gaaa058. pmid: 32866233
[12]	Zhou Y, Gan G. The levels of peripheral blood TNF-α, Decorin and neutrophils MAPK1 mRNA levels of patients with preeclampsia and their clinical significance[J]. J Matern Fetal Neonatal Med, 2023, 36(1):2183745. doi: 10.1080/14767058.2023.2183745.
[13]	Malhotra A, Rocha A, Yawno T, et al. Neuroprotective effects of maternal melatonin administration in early-onset placental insufficiency and fetal growth restriction[J]. Pediatr Res, 2024, 95(6):1510-1518. doi: 10.1038/s41390-024-03027-4. pmid: 38225450
[14]	Murthi P, van Zanten DE, Eijsink JJ, et al. Decorin expression is decreased in first trimester placental tissue from pregnancies with small for gestation age infants at birth[J]. Placenta, 2016, 45:58-62. doi: 10.1016/j.placenta.2016.07.008. pmid: 27577711
[15]	Araujo Júnior E, Zamarian AC, Caetano AC, et al. Physiopathology of late-onset fetal growth restriction[J]. Minerva Obstet Gynecol, 2021, 73(4):392-408. doi: 10.23736/S2724-606X.21.04771-7.
[16]	Cağlar M, Yavuzcan A, Göksu M, et al. Decorin: a possible marker for fetal growth restriction[J]. Gynecol Endocrinol, 2014, 30(2):141-144. doi: 10.3109/09513590.2013.860125. pmid: 24256371
[17]	Ghafoor S. Current and Emerging Strategies for Prediction and Diagnosis of Prelabour Rupture of the Membranes: A Narrative Review[J]. Malays J Med Sci, 2021, 28(3):5-17. doi: 10.21315/mjms2021.28.3.2.
[18]	Wang L, Wang H, Luo J, et al. Decorin promotes decidual M1-like macrophage polarization via mitochondrial dysfunction resulting in recurrent pregnancy loss[J]. Theranostics, 2022, 12(17):7216-7236. doi: 10.7150/thno.78467. pmid: 36438479
[19]	Ayvacı H, Koç N, Tarhan N, et al. Decorin expression in tubal ectopic and intrauterine pregnancies[J]. J Gynecol Obstet Hum Reprod, 2021, 50(10):102213. doi: 10.1016/j.jogoh.2021.102213.
[20]	Park BS, Lee J, Jun JH. Decorin: a multifunctional proteoglycan involved in oocyte maturation and trophoblast migration[J]. Clin Exp Reprod Med, 2021, 48(4):303-310. doi: 10.5653/cerm.2021.05071. pmid: 34875737
[21]	Appunni S, Rubens M, Ramamoorthy V, et al. Biglycan: an emerging small leucine-rich proteoglycan (SLRP) marker and its clinicopathological significance[J]. Mol Cell Biochem, 2021, 476(11):3935-3950. doi: 10.1007/s11010-021-04216-z. pmid: 34181183
[22]	Underhill LA, Avalos N, Tucker R, et al. Serum Decorin and Biglycan as Potential Biomarkers to Predict PPROM in Early Gestation[J]. Reprod Sci, 2020, 27(8):1620-1626. doi: 10.1007/s43032-020-00192-9. pmid: 32436194
[23]	Mennella JM, Underhill LA, Collis S, et al. Serum Decorin, Biglycan, and Extracellular Matrix Component Expression in Preterm Birth[J]. Reprod Sci, 2021, 28(1):228-236. doi: 10.1007/s43032-020-00251-1.
[24]	Briffa JF, Bevens W, Gravina S, et al. Pregnant biglycan knockout mice have altered cardiorenal adaptations and a shorter gestational length, but do not develop a pre-eclamptic phenotype[J]. Placenta, 2022, 119:52-62. doi: 10.1016/j.placenta.2022.02.002. pmid: 35150975
[25]	Bano S, Fatima S, Ahamad S, et al. Identification and characterization of a novel isoform of heparin cofactor Ⅱ in human liver[J]. IUBMB Life, 2020, 72(10):2180-2193. doi: 10.1002/iub.2361.
[26]	Pantham P, Armstrong DL, Bodnariuc J, et al. Transcriptomic profiling of fetal membranes of mice deficient in biglycan and decorin as a model of preterm birth[J]. Biol Reprod, 2021, 104(3):611-623. doi: 10.1093/biolre/ioaa205.
[27]	de Miranda de Araujo LB, Horgan CE, Aron A, et al. Compensatory fetal membrane mechanisms between biglycan and decorin in inflammation[J]. Mol Reprod Dev, 2015, 82(5):387-396. doi: 10.1002/mrd.22488. pmid: 25914258
[28]	Maiti G, Ashworth S, Choi T, et al. Molecular cues for immune cells from small leucine-rich repeat proteoglycans in their extracellular matrix-associated and free forms[J]. Matrix Biol, 2023, 123:48-58. doi: 10.1016/j.matbio.2023.10.001. pmid: 37793508
[29]	Smith MM, Melrose J. Lumican, a Multifunctional Cell Instructive Biomarker Proteoglycan Has Novel Roles as a Marker of the Hypercoagulative State of Long Covid Disease[J]. Int J Mol Sci, 2024, 25(5):2825. doi: 10.3390/ijms25052825.
[30]	Kedem A, Ulanenko-Shenkar K, Yung Y, et al. The Involvement of Lumican in Human Ovulatory Processes[J]. Reprod Sci, 2022, 29(2):366-373. doi: 10.1007/s43032-021-00650-y.
[31]	Isani G, Ferlizza E, Cuoghi A, et al. Identification of the most abundant proteins in equine amniotic fluid by a proteomic approach[J]. Anim Reprod Sci, 2016, 174:150-160. doi: 10.1016/j.anireprosci.2016.10.003. pmid: 27769536
[32]	Liu C, Hu Y, Wang Z, et al. The Downregulation of Placental Lumican Promotes the Progression of Preeclampsia[J]. Reprod Sci, 2021, 28(11):3147-3154. doi: 10.1007/s43032-021-00660-w. pmid: 34231169
[33]	Wang C, Yang C, Wang X, et al. ceRNA Network and Functional Enrichment Analysis of Preeclampsia by Weighted Gene Coexpression Network Analysis[J]. Comput Math Methods Med, 2022,2022:5052354. doi: 10.1155/2022/5052354.
[34]	Kang Q, Li W, Xiao J, et al. Identification of potential crucial genes associated with early-onset preeclampsia via bioinformatic analysis[J]. Pregnancy Hypertens, 2021, 24:27-36. doi: 10.1016/j.preghy.2021.02.007. pmid: 33640831
[35]	Hsu TY, Tsai KW, Lan KC, et al. Identifying the potential protein biomarkers of preterm birth in amniotic fluid[J]. Taiwan J Obstet Gynecol, 2020, 59(3):366-371. doi: 10.1016/j.tjog.2020.03.005.
[36]	Zheng Z, Granado HS, Li C. Fibromodulin, a Multifunctional Matricellular Modulator[J]. J Dent Res, 2023, 102(2):125-134. doi: 10.1177/00220345221138525.
[37]	Jiang QL, Xu JY, Yao QP, et al. Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin[J]. Cell Mol Biol Lett, 2024, 29(1):2. doi: 10.1186/s11658-023-00523-z.
[38]	Zhao F, Bai Y, Xiang X, et al. The role of fibromodulin in inflammatory responses and diseases associated with inflammation[J]. Front Immunol, 2023,14:1191787. doi: 10.3389/fimmu.2023.1191787.
[39]	Walimbe T, Panitch A. Proteoglycans in Biomedicine: Resurgence of an Underexploited Class of ECM Molecules[J]. Front Pharmacol, 2019,10:1661. doi: 10.3389/fphar.2019.01661.
[40]	Favaro RR, Raspantini PR, Salgado RM, et al. Long-term type 1 diabetes alters the deposition of collagens and proteoglycans in the early pregnant myometrium of mice[J]. Histol Histopathol, 2015, 30(4):435-444. doi: 10.14670/HH-30.435. pmid: 25196145