Altered release of thrombomodulin and HMGB1 in the placenta complicated with preeclampsia
Copyright © 2024 Elsevier Ltd. All rights reserved..
INTRODUCTION: Preeclampsia (PE) is a severe pregnancy complication due to placental dysfunction. Thrombomodulin (TM), a glycoprotein expressed on the trophoblast cell membrane, plays an organ-protective role in the placenta by regulating coagulation and inflammation. TM-mediated regulation of High Mobility Group Box1(HMGB1) is an essential mechanism that contributes to placental homeostasis and prevents pregnancy complications in mice. Here, we aimed to clarify the role of placental TM and HMGB1 in the pathophysiology of human PE.
METHODS AND RESULTS: In this study, maternal blood serum and placental tissue were obtained from 72 PE patients and 110 normal controls. Soluble TM(sTM) and HMGB1 levels in the maternal serum were assessed. The placental TM and HMGB1 expression levels were evaluated using immunohistochemistry and qPCR. Serum sTM and HMGB1 levels gradually increased with gestational age in normal pregnancies; however, both circulating sTM and HMGB1 levels were significantly higher in the PE group. Serum HMGB1/sTM ratio was elevated in PE patients compared to that in normal controls, which correlated positively with the clinical severity of PE. The immunohistochemistry analysis revealed the loss of TM and the increase in extranuclear HMGB1. TM mRNA expression was diminished in PE placentas, which negatively correlated with soluble fms-like tyrosine kinase-1 (sFlt-1) expression.
DISCUSSION: The increase in circulating sTM and HMGB1 could be attributed to the enhanced placental TM shedding in PE patients. The molecular events mediated by the imbalance in the placental TM and HMGB1 levels could be an underlying feature of PE; maternal serum HMGB1/sTM ratio could reflect this status.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:148 |
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| Enthalten in: |
Placenta - 148(2024) vom: 25. März, Seite 12-19 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Oda, Hiroko [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.03.2024 Date Revised 19.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.placenta.2024.01.016 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368200299 |
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| 245 | 1 | 0 | |a Altered release of thrombomodulin and HMGB1 in the placenta complicated with preeclampsia |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
| 520 | |a INTRODUCTION: Preeclampsia (PE) is a severe pregnancy complication due to placental dysfunction. Thrombomodulin (TM), a glycoprotein expressed on the trophoblast cell membrane, plays an organ-protective role in the placenta by regulating coagulation and inflammation. TM-mediated regulation of High Mobility Group Box1(HMGB1) is an essential mechanism that contributes to placental homeostasis and prevents pregnancy complications in mice. Here, we aimed to clarify the role of placental TM and HMGB1 in the pathophysiology of human PE | ||
| 520 | |a METHODS AND RESULTS: In this study, maternal blood serum and placental tissue were obtained from 72 PE patients and 110 normal controls. Soluble TM(sTM) and HMGB1 levels in the maternal serum were assessed. The placental TM and HMGB1 expression levels were evaluated using immunohistochemistry and qPCR. Serum sTM and HMGB1 levels gradually increased with gestational age in normal pregnancies; however, both circulating sTM and HMGB1 levels were significantly higher in the PE group. Serum HMGB1/sTM ratio was elevated in PE patients compared to that in normal controls, which correlated positively with the clinical severity of PE. The immunohistochemistry analysis revealed the loss of TM and the increase in extranuclear HMGB1. TM mRNA expression was diminished in PE placentas, which negatively correlated with soluble fms-like tyrosine kinase-1 (sFlt-1) expression | ||
| 520 | |a DISCUSSION: The increase in circulating sTM and HMGB1 could be attributed to the enhanced placental TM shedding in PE patients. The molecular events mediated by the imbalance in the placental TM and HMGB1 levels could be an underlying feature of PE; maternal serum HMGB1/sTM ratio could reflect this status | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a High mobility group Box1 (HMGB1) | |
| 650 | 4 | |a Preeclampsia | |
| 650 | 4 | |a Pregnancy complication | |
| 650 | 4 | |a Serum biomarker | |
| 650 | 4 | |a Thrombomodulin | |
| 650 | 7 | |a HMGB1 Protein |2 NLM | |
| 650 | 7 | |a Placenta Growth Factor |2 NLM | |
| 650 | 7 | |a 144589-93-5 |2 NLM | |
| 650 | 7 | |a Thrombomodulin |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor Receptor-1 |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a THBD protein, human |2 NLM | |
| 650 | 7 | |a HMGB1 protein, human |2 NLM | |
| 700 | 1 | |a Nagamatsu, Takeshi |e verfasserin |4 aut | |
| 700 | 1 | |a Iriyama, Takayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Osuga, Yutaka |e verfasserin |4 aut | |
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