The Role of Thrombospondin-1 in the Pathogenesis of Preeclampsia

doi:10.12280/gjfckx.20250051

Abstract

Abstract:

Preeclampsia (PE) is a pregnancy-specific disorder and one of the leading causes of maternal mortality and neonatal morbidity. To date, the etiology and pathogenesis of PE remain incompletely elucidated. Insufficient trophoblast invasion leading to impaired uterine spiral artery remodeling, aberrant placental development, and vascular endothelial dysfunction are key factors contributing to the pathogenesis of PE. Thrombospondin-1 (TSP-1), a multi-domain and multi-functional extracellular matrix glycoprotein secreted by various human cells, interacts with multiple cell surface receptors and plays a role in regulating diverse physiological and pathological processes, including angiogenesis, inflammatory responses, platelet activation, cellular invasion, and immune responses, and the occurrence and development of hypertension and hyperlipidemia. Recent studies have demonstrated elevated expression levels of TSP-1 in both the placenta and maternal serum of patients with PE. Consequently, TSP-1 may be one of the contributing factors to the pathogenesis of PE. This review aims to summarize the role of TSP-1 in the pathophysiology of PE, providing new ideas for its diagnosis and treatment.

Key words: Pre-eclampsia, Thrombospondin 1, Endothelium, vascular, Oxidative stress, Neovascularization, physiologic

REN Sheng, WANG Yong-hong. The Role of Thrombospondin-1 in the Pathogenesis of Preeclampsia[J]. Journal of International Obstetrics and Gynecology, 2025, 52(3): 275-279.

References 31

[1]	Cheng K, Cui J, Zhou W, et al. miRNA-141-5p Affects the Levels of Neutrophil Elastase in Preeclampsia by Regulating MAPK1[J]. Maternal-Fetal Medicine, 2022, 4(4):238-244. doi: 10.1097/FM9.0000000000000169.
[2]	Shan Y, Hou B, Wang J, et al. Exploring the role of exosomal MicroRNAs as potential biomarkers in preeclampsia[J]. Front Immunol, 2024,15:1385950. doi: 10.3389/fimmu.2024.1385950.
[3]	Kale A, Rogers NM, Ghimire K. Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine[J]. Int J Mol Sci, 2021, 22(8):4062. doi: 10.3390/ijms22084062.
[4]	Hassan HM, Liang X, Xin J, et al. Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure[J]. BMC Med, 2024, 22(1):95. doi: 10.1186/s12916-024-03318-x. pmid: 38439091
[5]	Liu B, Yang H, Song YS, et al. Thrombospondin-1 in vascular development, vascular function, and vascular disease[J]. Semin Cell Dev Biol, 2024, 155(Pt B):32-44. doi: 10.1016/j.semcdb.2023.07.011.
[6]	Tabary M, Gheware A, Peñaloza HF, et al. The matricellular protein thrombospondin-1 in lung inflammation and injury[J]. Am J Physiol Cell Physiol, 2022, 323(3):C857-C865. doi: 10.1152/ajpcell.00182.2022.
[7]	Duan FM, Fu LJ, Wang YH, et al. THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia[J]. Genes Dis, 2021, 8(3):353-363. doi: 10.1016/j.gendis.2020.05.007. pmid: 33997182
[8]	Li Y, Han B, Salmeron AG, et al. Estrogen-Induced Uterine Vasodilation in Pregnancy and Preeclampsia[J]. Matern Fetal Med, 2022, 4(1):52-60. doi: 10.1097/FM9.0000000000000132.
[9]	Azmi MB, Nasir MF, Asif U, et al. Analyzing molecular signatures in preeclampsia and fetal growth restriction: Identifying key genes, pathways, and therapeutic targets for preterm birth[J]. Front Mol Biosci, 2024,11:1384214. doi: 10.3389/fmolb.2024.1384214.
[10]	Isenberg JS, Roberts DD. THBS1 (thrombospondin-1)[J]. Atlas Genet Cytogenet Oncol Haematol, 2020, 24(8):291-299. doi: 10.4267/2042/70774.
[11]	Li ZH, Li X, Li FF, et al. The roles of ADAMDEC1 in trophoblast differentiation during normal pregnancy and preeclampsia[J]. Mol Hum Reprod, 2022, 28(5):gaac014. doi: 10.1093/molehr/gaac014.
[12]	Kornacki J, Olejniczak O, Sibiak R, et al. Pathophysiology of Pre-Eclampsia-Two Theories of the Development of the Disease[J]. Int J Mol Sci, 2023, 25(1):307. doi: 10.3390/ijms25010307.
[13]	Sharma K, Chanana N, Mohammad G, et al. Hypertensive Patients Exhibit Enhanced Thrombospondin-1 Levels at High-Altitude[J]. Life(Basel), 2021, 11(9):893. doi: 10.3390/life11090893.
[14]	Wang P, Wu J, Wang Q, et al. Baicalin inhibited both the Furin/TGFβ1/Smad3/TSP-1 pathway in endothelial cells and the AKT/Ca²⁺/ROS pathway in platelets to ameliorate inflammatory coagulopathy[J]. Eur J Pharmacol, 2023,949:175674. doi: 10.1016/j.ejphar.2023.175674.
[15]	Xu FF, Zheng F, Chen Y, et al. Role of thrombospondin-1 in high-salt-induced mesenteric artery endothelial impairment in rats[J]. Acta Pharmacol Sin, 2024, 45(3):545-557. doi: 10.1038/s41401-023-01181-9.
[16]	Zhu ML, Fan JX, Guo YQ, et al. Protective effect of alizarin on vascular endothelial dysfunction via inhibiting the type 2 diabetes-induced synthesis of THBS1 and activating the AMPK signaling pathway[J]. Phytomedicine, 2024,128:155557. doi: 10.1016/j.phymed.2024.155557.
[17]	Sun J, Ge X, Wang Y, et al. USF2 knockdown downregulates THBS1 to inhibit the TGF-β signaling pathway and reduce pyroptosis in sepsis-induced acute kidney injury[J]. Pharmacol Res, 2022,176:105962. doi: 10.1016/j.phrs.2021.105962.
[18]	Liu K, Wang J, Gao X, et al. C1q/TNF-Related Protein 9 Inhibits Coxsackievirus B3-Induced Injury in Cardiomyocytes through NF-κB and TGF-beta1/Smad2/3 by Modulating THBS1[J]. Mediators Inflamm, 2020,2020:2540687. doi: 10.1155/2020/2540687.
[19]	Lv Y, Huang Y, Fan H, et al. 17β-Estradiol inhibits hydrogen peroxide-induced senescence and apoptosis in human umbilical vein endothelial cells by regulating the THBS1/TGF-β/Smad axis[J]. Mol Cell Endocrinol, 2024,580:112111. doi: 10.1016/j.mce.2023.112111.
[20]	Grenier C, Caillon A, Munier M, et al. Dual Role of Thrombospondin-1 in Flow-Induced Remodeling[J]. Int J Mol Sci, 2021, 22(21):12086. doi: 10.3390/ijms222112086.
[21]	Soobryan N, Kumar A, Moodley J, et al. The role and expression of pro/antiangiogenic factors and microRNAs in gestational hypertension and pre-eclampsia[J]. Eur J Obstet Gynecol Reprod Biol, 2023, 290:38-42. doi: 10.1016/j.ejogrb.2023.09.012. pmid: 37716201
[22]	Ju Y, Tang Z, Dai X, et al. Protection against light-induced retinal degeneration via dual anti-inflammatory and anti-angiogenic functions of thrombospondin-1[J]. Br J Pharmacol, 2022, 179(9):1938-1961. doi: 10.1111/bph.15303.
[23]	Liao F, Liao Z, Zhang T, et al. ECFC-derived exosomal THBS1 mediates angiogenesis and osteogenesis in distraction osteogenesis via the PI3K/AKT/ERK pathway[J]. J Orthop Translat, 2022, 37:12-22. doi: 10.1016/j.jot.2022.08.004.
[24]	Szczerba K, Stokowa-Soltys K. What Is the Correlation between Preeclampsia and Cancer? The Important Role of Tachykinins and Transition Metal Ions[J]. Pharmaceuticals (Basel), 2023, 16(3):366. doi: 10.3390/ph16030366.
[25]	Liu Z, Wen J, Hu F, et al. Thrombospondin-1 induced programmed death-ligand 1-mediated immunosuppression by activating the STAT3 pathway in osteosarcoma[J]. Cancer Sci, 2022, 113(2):432-445. doi: 10.1111/cas.15237.
[26]	Morandi V, Petrik J, Lawler J. Endothelial Cell Behavior Is Determined by Receptor Clustering Induced by Thrombospondin-1[J]. Front Cell Dev Biol, 2021,9:664696. doi: 10.3389/fcell.2021.664696.
[27]	Yu X, Wu H, Yang Y, et al. Placental Development and Pregnancy-Associated Diseases[J]. Maternal-Fetal Medicine, 2022, 4(1):36-51. doi: 10.1097/FM9.0000000000000134.
[28]	Li J, Feng H, Zhu J, et al. Gastric cancer derived exosomal THBS1 enhanced Vγ9Vδ2 T-cell function through activating RIG-I-like receptor signaling pathway in a N6-methyladenosine methylation dependent manner[J]. Cancer Lett, 2023,576:216410. doi: 10.1016/j.canlet.2023.216410.
[29]	Ma Y, Ye S, Liu Y, et al. Interferon regulatory factor 1 mediated inhibition of Treg cell differentiation induces maternal-fetal immune imbalance in preeclampsia[J]. Int Immunopharmacol, 2024,141:112988. doi: 10.1016/j.intimp.2024.112988.
[30]	Xiao Q, Li X, Liu C, et al. Improving cancer immunotherapy via co-delivering checkpoint blockade and thrombospondin-1 downregulator[J]. Acta Pharm Sin B, 2023, 13(8):3503-3517. doi: 10.1016/j.apsb.2022.07.012.
[31]	Li W, Zeng Q, Wang B, et al. Oxidative stress promotes oral carcinogenesis via Thbs1-mediated M1-like tumor-associated macrophages polarization[J]. Redox Biol, 2024,76:103335. doi: 10.1016/j.redox.2024.103335.