Journal of Shanghai Jiao Tong University (Medical Science) >

2024 , Vol. 44 >Issue 11: 1383 - 1390

DOI: https://doi.org/10.3969/j.issn.1674-8115.2024.11.005

Basic research

Expression of MTA1 in preeclamptic placental tissue and its effects on trophoblast function

  • Yao GENG ,
  • Yang ZHANG ,
  • Jie ZHAO ,
  • Wei LI ,
  • Guoqing CAI
Expand
  • 1.College of Life Science, Northwest University, Xi′an 710069, China
    2.Department of Human Anatomy, Histology and Embryology, Basic Medical Science Academy, Air Force Military Medical University, Xi′an 710032, China
    3.Department of Gynaecology and Obstetrics, Xijing Hospital, Air Force Military Medical University, Xi′an 710032, China
CAI Guoqing, E-mail: 184634529@qq.com.

Received date: 2024-01-02

  Accepted date: 2024-05-13

  Online published: 2024-11-28

Supported by

National Natural Science Foundation of China(31971070);General Projects of Shaanxi Provincial Key R & D Plan(2022SF-241)

Fold

Abstract

Objective ·To investigate the expression of metastasis-associated protein 1 (MTA1) in placental tissues of preeclampsia (PE) patients and its impact on trophoblast cell function. Methods ·Placental specimens were collected from pregnant women with PE (PE group, 20 cases) patients and healthy pregnant women as controls (control group, 35 cases). Western blotting and immunofluorescent double staining were performed to analyze the expression changes of MTA1. The human first-trimester placental trophoblast cell line HTR8/SVneo was cultured, and the cell migration ability was assessed through wound healing assay. The cell invasion ability was detected using Transwell invasion assay. Under hypoxic conditions simulating the invasion of extravillous trophoblasts into the uterus, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyze the mRNA expression of hypoxia-induced matrix metalloproteinases (MMP-2 and MMP-9), thus assessing their secretion levels. An extravillous trophoblast explant model was constructed to assess the overall villus outgrowth capacity of the explants. Immunohistochemistry (IHC) was performed to confirm the presence of the endothelial marker CD31 for placental angiogenesis analysis in mice. Fifteen Mta1-/- female mice and fifteen wild-type C57 female mice were mated with wild-type male C57 mice for fertility testing. Results ·Western blotting revealed significantly decreased expression of MTA1 protein in placental tissues of the PE group compared to the control group. Immunofluorescent double staining showed that MTA1 was mainly localized in the nuclei of trophoblast cells. The wound healing assay demonstrated that HTR8/SVneo with stable MTA1 knockdown exhibited weaker cell migration ability compared to the control group (P=0.002). The Transwell invasion assay demonstrated a marked decrease in invasiveness in MTA1-knockdown cells, significantly lower than the control group (P=0.015). Hypoxia-induced expression levels of matrix metalloproteinases MMP-2 and MMP-9 were significantly reduced (P=0.020, P=0.003). After MTA1 knockdown, the overall villus outgrowth capacity of the explants was decreased compared to the control group (P=0.003). IHC results showed that CD31 expression in the placenta of Mta1-/- female mice was significantly lower than that of wild-type female mice (P=0.004). The litter size of Mta1-/- female mice was significantly reduced (P=0.000). Conclusion ·The expression level of MTA1 is closely related to PE. Endogenous MTA1 may be involved in trophoblast invasion into the endometrium and villous capillary remodeling.

Key words： preeclampsia (PE); metastasis-associated protein 1 (MTA1); extravillous trophoblast (EVT)

Cite this article

Yao GENG , Yang ZHANG , Jie ZHAO , Wei LI , Guoqing CAI . Expression of MTA1 in preeclamptic placental tissue and its effects on trophoblast function[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024 , 44(11) : 1383 -1390 . DOI: 10.3969/j.issn.1674-8115.2024.11.005

References

1 VON DADELSZEN P, MAGEE L A. Pre-eclampsia: an update[J]. Curr Hypertens Rep, 2014, 16(8): 454.
2 NAKASHIMA A, CHENG S B, IKAWA M, et al. Evidence for lysosomal biogenesis proteome defect and impaired autophagy in preeclampsia[J]. Autophagy, 2020, 16(10): 1771-1785.
3 ZHANG H, HE Y, WANG J X, et al. MiR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia[J]. Redox Biol, 2020, 29: 101402.
4 TABRIZI M E A, GUPTA J K, GROSS S R. Ezrin and its phosphorylated Thr567 form are key regulators of human extravillous trophoblast motility and invasion[J]. Cells, 2023, 12(5): 711.
5 GHANTA K S, LI D Q, ESWARAN J, et al. Gene profiling of MTA1 identifies novel gene targets and functions[J]. PLoS One, 2011, 6(2): e17135.
6 QIN J H, KE Z Y, ZHOU Q, et al. Metastasis-associated protein 1 deficiency results in compromised pulmonary alveolar capillary angiogenesis in mice[J]. Med Sci Monit, 2017, 23: 3932-3941.
7 LI D Q, PAKALA S B, REDDY S D N, et al. Metastasis-associated protein 1 is an integral component of the circadian molecular machinery[J]. Nat Commun, 2013, 4: 2545.
8 VALERO-PACHECO N, TANG E K, MASSRI N, et al. Maternal IL-33 critically regulates tissue remodeling and type 2 immune responses in the uterus during early pregnancy in mice[J]. Proc Natl Acad Sci USA, 2022, 119(35): e2123267119.
9 AFSAR B, ELSURER AFSAR R. The dilemma of sodium intake in preeclampsia: beneficial or detrimental?[J]. Nutr Rev, 2024, 82(3): 437-449.
10 BRüNING A, MAKOVITZKY J, GINGELMAIER A, et al. The metastasis-associated genes MTA1 and MTA3 are abundantly expressed in human placenta and chorionic carcinoma cells[J]. Histochem Cell Biol, 2009, 132(1): 33-38.
11 MA J, LI C, QIAN H, et al. MTA1: a vital modulator in prostate cancer[J]. Curr Protein Pept Sci, 2022, 23(7): 456-464.
12 BURGOLD T, BARBER M, KLOET S, et al. The Nucleosome Remodelling and Deacetylation complex suppresses transcriptional noise during lineage commitment[J]. EMBO J, 2019, 38(12): e100788.
13 LI W, WU Z Q, ZHAO J, et al. Transient protection from heat-stress induced apoptotic stimulation by metastasis-associated protein 1 in pachytene spermatocytes[J]. PLoS One, 2011, 6(10): e26013.
14 LI W, MA L, ZHAO J, et al. Expression profile of MTA1 in adult mouse tissues[J]. Tissue Cell, 2009, 41(6): 390-399.
15 LUIZON M R, PEREIRA D A, MAMEDE I, et al. Antihypertensive therapy responsiveness and adverse outcomes in preeclampsia: insights into molecular mechanisms underlying cardiovascular and renal complications[J]. Front Pharmacol, 2023, 14: 1281382.
16 SHI H, KONG R, MIAO X, et al. Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway[J]. Exp Biol Med (Maywood), 2023, 248(16): 1373-1382.
17 JIE Q, CHEN L, LIANG J, et al. Downregulated ETV4 inhibits the proliferation, migration, and invasion of trophoblast cells in preeclampsia[J]. Reproduction, 2023, 165(4): 373-381.
18 SUI S, ZHANG Y, HUANG Y. MicroRNA-378a-3p plays a regulatory role in trophoblast cell function in preeclampsia by targeting CMTM3[J]. Mol Cell Endocrinol, 2023, 576: 111997.
19 LI J, ZHANG J, WANG Y, et al. Synergistic inhibition of migration and invasion of breast cancer cells by dual docetaxel/quercetin-loaded nanoparticles via Akt/MMP-9 pathway[J]. Int J Pharm, 2017, 523(1): 300-309.
20 YIN X, TENG X, MA T Y, et al. RUNX2 recruits the NuRD(MTA1)/CRL4B complex to promote breast cancer progression and bone metastasis[J]. Cell Death Differ, 2022, 29: 2203-2217.
21 CANCEMI P, BUTTACAVOLI M, ROZ E, et al. Expression of α-enolase (ENO1), myc promoter-binding protein-1 (MBP-1) and matrix metalloproteinases (MMP-2 and MMP-9) reflect the nature and aggressiveness of breast tumors[J]. Int J Mol Sci, 2019, 20(16): E3952.
22 MYERS J E, MERCHANT S J, MACLEOD M, et al. MMP-2 levels are elevated in the plasma of women who subsequently develop preeclampsia[J]. Hypertens Pregnancy, 2005, 24(2): 103-115.
23 DING J, HUANG F, WU G, et al. MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2[J]. PLoS One, 2015, 10(3): e0120321.
24 LIN C, HE H, CUI N, et al. Decreased uterine vascularization and uterine arterial expansive remodeling with reduced matrix metalloproteinase-2 and-9 in hypertensive pregnancy[J]. Am J Physiol Heart Circ Physiol, 2020, 318(1): H165-H180.
25 CHU Y J, ZHU C Z, YUE C Y, et al. Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes the proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway[J]. Cell Biosci, 2021, 11(1): 182.
26 PEREA V, VINAGRE I, SERéS-NORIEGA T, et al. Impact of preeclampsia and parity on sex-based discrepancies in subclinical carotid atherosclerosis in type 1 diabetes[J]. J Clin Endocrinol Metab, 2024, 109(9): e1759-e1767.
27 CHAPPELL L C, DUCKWORTH S, SEED P T, et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study[J]. Circulation, 2013, 128(19): 2121-2131.
28 DUHIG K E, MYERS J, SEED P T, et al. Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial[J]. Lancet, 2019, 393(10183): 1807-1818.
29 CERDEIRA A S, O′SULLIVAN J, OHUMA E O, et al. Randomized interventional study on prediction of preeclampsia/eclampsia in women with suspected preeclampsia: INSPIRE[J]. Hypertension, 2019, 74(4): 983-990.
30 ZEISLER H, LLURBA E, CHANTRAINE F, et al. Predictive value of the sFlt-1: PLGF ratio in women with suspected preeclampsia[J]. N Engl J Med, 2016, 374(1): 13-22.
Options
Outlines

/

〈 〉