N-acetylglucosaminyltransferase V inhibits the invasion of trophoblast cells by attenuating MMP2/9 activity in early human pregnancy

Deng, Qinyin; Chen, Ying; Yin, Ning; Shan, Nan; Luo, Xin; Tong, Chao; Zhang, Hua; Baker, Philip N.; Liu, Xiru; Qi, Hongbo

doi:10.1016/j.placenta.2015.08.014

Cited by 31 publications

(41 citation statements)

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“…12 After the cultures were screened using puromycin, we obtained a stable HUVEC cell line in which the human MGAT5 gene was silenced; this cell line was then used in subsequent experiments.…”

Section: Rna Interference Targeting Mgat5 In Huvecs and Fak-erk Inhibmentioning

confidence: 99%

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The Role of MGAT5 in Human Umbilical Vein Endothelial Cells: Possible Relevance to the Pathological Mechanism of Preeclampsia

et al. 2017

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Preeclampsia (PE) is associated with shallow invasion of the trophoblast and insufficient remodeling of the uterine spiral artery. Glycosylation reactions are catalyzed by glycosyltransferases including N-acetylglucosaminyltransferase V (MGAT5) and accumulating evidence suggests that MGAT5 is correlated with the migration, proliferation, and survival of various cell types. Our previous study confirmed that MGAT5 is a negative regulator of trophoblast migration and invasion via the direct or indirect inhibition of matrix metalloproteinase 2/9 activity. The primary purpose of this study is to investigate the role of MGAT5 in the function of human umbilical vein endothelial cells (HUVECs) during the development of PE. We observed that MGAT5 was specifically localized within the decidual cells and endothelial cells in maternal decidual tissues. The expression of MGAT5 was elevated in PE placentas compared with the normal control placentas. Moreover, the expression of MGAT5 was increased in hypoxia-reoxygenation (H/R)-treated HUVECs. The knockdown of MGAT5 and PD98059 treatment significantly enhanced cell migration in vitro, promoted tube formation capacity, and inhibited apoptosis in H/R-exposed HUVECs. Our data suggest that oxidative stress induces the overexpression of MGAT5 via the regulation of the focal adhesion kinase-extracellular signal-regulated kinase signaling pathway, which, in turn, affects the function of endothelial cells, which then participates in the pathogenesis of PE.

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Section: Rna Interference Targeting Mgat5 In Huvecs and Fak-erk Inhibmentioning

confidence: 99%

“…We also found a role for MGAT5 in the inhibition of human trophoblast cell invasion and migration during early pregnancy via the direct or indirect regulation of matrix metalloproteinase (MMP) 2/9 activity. 12 However, the role of MGAT5 in the pathogenesis of PE requires further elucidation.…”

Section: Introductionmentioning

confidence: 99%

The Role of MGAT5 in Human Umbilical Vein Endothelial Cells: Possible Relevance to the Pathological Mechanism of Preeclampsia

et al. 2017

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“…The process may demonstrate an important mechanism in which EG-VEGF modulates trophoblast invasion on pregnancy-related pathophysiology, such as embryo implantation, placental development, preeclampsia, and IUGR. MMP 9 expression and impairment of MMP 2/MMP 9 activity have been found to be important mechanisms for several genes to impair trophoblast invasiveness in preeclampsia, such as the response gene to complement 32 (RGC32), caudalrelated homeobox transcription factor 2 (CDX2), Nacetylglucosaminyltransferase V(MGAT5), growth arrest and DNA damage-inducible 45 alpha (Gadd45a), oxidative stressinduced C/EBPb, and preimplantation factor (PIF) [43][44][45][46][47][48]. Furthermore, some of the signalings underlying trophoblast invasion have been shown to occur through mitogen-activated protein kinase (MAPK), focal adhesion kinase (FAK), the phosphoinositide-3-kinase (PI3K)-Akt pathway, Wingless (Wnt) signaling, or the Janus-kinase signal transducer, and activator of transcription (JAK-STAT) [43,44,47,48].…”

Section: Discussionmentioning

confidence: 99%

miR‐346 and miR‐582‐3p‐regulated EG‐VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9

Tsai

et al. 2016

BioFactors

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Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an important regulator for embryo implantation and placental development, and is clinically associated with several obstetric disorders related to insufficient or inappropriate trophoblast invasion, such as recurrent abortion, preeclampsia, and intrauterine fetal growth restriction. This study was performed to identify the microRNAs targeting EG-VEGF, and evaluate the regulatory effect on trophoblast biology. miR-346 and miR-582-3p were initially identified via bioinformatic tools, and their specific binding sites on the EG-VEGF 3'UTR were further confirmed using dual luciferase and a co-transfection assays. miR-346 and miR-582-3p were demonstrated not only to suppress EG-VEGF expression, but also inhibit trophoblast invasion and migration in the JAR and HTR-8/SVneo cell lines. We further evaluated the effect of microRNAs in HTR-8/SVneo cells coexpressing EG-VEGF and miR-346 or miR-582-3p on matrix metalloproteinase (MMP 2 and MMP 9) and the tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2) using RT-PCR, western blotting and gelatin zymography. TIMP 1 and TIMP 2 were not affected by the two microRNAs, whereas the expressions and activities of MMP 2 and MMP 9 were significantly downregulated, which in turn inhibited the invasion ability of trophoblasts. In conclusion, miR-346 and miR-582-3p regulate EG-VEGF-induced trophoblast invasion through repressing MMP 2 and MMP 9, and may become novel diagnostic biomarkers or therapeutic targets for EG-VEGF-related obstetric disorders. © 2016 BioFactors, 43(2):210-219, 2017.

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“…Ключевыми факторами протеолиза при плацентации являются ферменты группы желатиназ -матриксные металлопротеиназы (MMPs) и их тканевые ингибиторы (TIMPs) [7][8][9]. В ряде работ показано, что уровни металлопротеиназ 2-го и 9-го типа (MMP-2, MMP-9) значительно выше в сыворотке у женщин с врастанием плаценты, чем у небеременных и при физиологически протекающей беременности [10,11].…”

Section: Introductionunclassified

“…Концентрации TIMPs зависят от концентраций MMPs в тканях и внеклеточной жидкости. TIMPs ограничивают протеолитическую активность MMPs в фокальном околоклеточном пространстве [10][11][12]. TIMPs содержатся в соединительной ткани, отличаются по своей специфичности ингибирования желатиназ, наиболее активны TIMP-1 к MMP-9 и TIMP-2 к MMP-2.…”

Section: Introductionunclassified

Placenta Accreta Forecasting Using Serum Marker Values

Lukashevich¹,

Aksenenko²,

Ap³

et al. 2020

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Цель исследования: изучение некоторых звеньев патогенеза врастания плаценты, а также определение сывороточных концентраций маркеров цитотрофобластической инвазии: матриксных металлопротеиназ 2-го и 9-го типа (MMP-2 и MMP-9), их ингибиторов (TIMP-1 и TIMP-2), кисспептина 1-и возможности использования их в качестве предикторов placenta accreta. Дизайн: сравнительное исследование. Материалы и методы. В исследование включены 150 женщин: 50 c диагнозом врастания предлежащей плаценты (основная группа), 50 с предлежанием плаценты без ее врастания (группа сравнения) и 50 родоразрешенных путем кесарева сечения по показаниям, не связанным с патологической плацентацией (контрольная группа). Материалом для изучения являлась сыворотка крови. При исследовании использовался гетерогенный иммуноферментный анализ. Материал для иммуногистохимического исследования брался интраоперационно: иссекались фрагменты миометрия и базальной оболочки, участок из центра плаценты. Результаты. У беременных с врастанием плаценты отмечается значимое (p < 0,05) повышение уровней MMP-2, MMP-9, TIMP-1, TIMP-2 и кисспептина 1 при сравнении распределения средних концентраций биомаркеров в сыворотке крови с таковыми в контрольной группе. Исходя из полученных нами данных, критическими величинами следует признать 380,8 пкг/мл для MMP-2; 240,1 нг/мл для MMP-9; 8,5 нг/мл для TIMP-1; 6,1 нг/мл для TIMP-2 и 145,2 пкг/мл для кисспептина 1. При превышении указанных концентраций отмечается статистически значимая (p < 0,05) корреляция с вероятностью патологической инвазии плаценты и ее врастанием. При соотношении концентраций MMP-9/TIMP-1 менее 49,9 выявлена значимая (p < 0,05) корреляция с врастанием плаценты при сравнении показателей женщин с placenta accreta и с предлежанием плаценты без врастания. Заключение. Полученные данные позволяют отнести MMP-2, MMP-9, TIMP-1, TIMP-2, кисспептин 1 к сывороточным предикторам врастания плаценты. Они с точностью 81,4%, чувствительностью 78,8% и специфичностью 84,0% прогнозируют возникновение во время беременности патологической плацентарной инвазии-врастания плаценты. Ключевые слова: врастание плаценты, матриксная металлопротеиназа, MMP-9, MMP-2, ингибитор матриксной металлопротеиназы, TIMP-1, TIMP-2, кисспептин 1, инвазия цитотрофобласта, иммуноферментный анализ.

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N-acetylglucosaminyltransferase V inhibits the invasion of trophoblast cells by attenuating MMP2/9 activity in early human pregnancy

Cited by 31 publications

References 41 publications

The Role of MGAT5 in Human Umbilical Vein Endothelial Cells: Possible Relevance to the Pathological Mechanism of Preeclampsia

The Role of MGAT5 in Human Umbilical Vein Endothelial Cells: Possible Relevance to the Pathological Mechanism of Preeclampsia

miR‐346 and miR‐582‐3p‐regulated EG‐VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9

Placenta Accreta Forecasting Using Serum Marker Values

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