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Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels.
Cell Physiol Biochem 2018; 45(3):1013-1022CP

Abstract

BACKGROUND/AIMS

Neuropathy target esterase (NTE, also known as neurotoxic esterase) is proven to deacylate phosphatidylcholine (PC) to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE)-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE.

METHODS

NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method.

RESULTS

NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels.

CONCLUSIONS

Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

Authors+Show Affiliations

Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China. Department of Reproductive Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China.Department of Obstetrics and Gynecology, JiangXi Province People's Hospital, Nanchang, China.Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China.Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China.Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China.Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China.Jiangxi Provincial Key Laboratory of Reproductive Physiology and Pathology, Medical Experimental Teaching Center, Nanchang University, Nanchang, China.Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China. Jiangxi Provincial Key Laboratory of Reproductive Physiology and Pathology, Medical Experimental Teaching Center, Nanchang University, Nanchang, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29428958

Citation

Zhong, Ting, et al. "Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion Via Modulating MMP-9 Levels." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 45, no. 3, 2018, pp. 1013-1022.
Zhong T, Chen J, Ling Y, et al. Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels. Cell Physiol Biochem. 2018;45(3):1013-1022.
Zhong, T., Chen, J., Ling, Y., Yang, B., Xie, X., Yu, D., ... Kuang, H. (2018). Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 45(3), pp. 1013-1022. doi:10.1159/000487296.
Zhong T, et al. Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion Via Modulating MMP-9 Levels. Cell Physiol Biochem. 2018;45(3):1013-1022. PubMed PMID: 29428958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels. AU - Zhong,Ting, AU - Chen,Jiaxiang, AU - Ling,Yan, AU - Yang,Bei, AU - Xie,Xingxing, AU - Yu,Dainan, AU - Zhang,Dalei, AU - Ouyang,Jiexiu, AU - Kuang,Haibin, Y1 - 2018/02/05/ PY - 2017/10/13/received PY - 2018/01/16/accepted PY - 2018/2/13/pubmed PY - 2018/3/20/medline PY - 2018/2/12/entrez KW - Invasion KW - Neuropathy target esterase KW - Placenta KW - Preeclampsia KW - Trophoblast SP - 1013 EP - 1022 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 45 IS - 3 N2 - BACKGROUND/AIMS: Neuropathy target esterase (NTE, also known as neurotoxic esterase) is proven to deacylate phosphatidylcholine (PC) to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE)-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. METHODS: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. RESULTS: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. CONCLUSIONS: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/29428958/Down_Regulation_of_Neuropathy_Target_Esterase_in_Preeclampsia_Placenta_Inhibits_Human_Trophoblast_Cell_Invasion_via_Modulating_MMP_9_Levels_ L2 - https://www.karger.com?DOI=10.1159/000487296 DB - PRIME DP - Unbound Medicine ER -