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HMGA1 Is a Potential Driver of Preeclampsia Pathogenesis by Interference with Extravillous Trophoblasts Invasion

Journal

BIOMOLECULES
Volume 11, Issue 6, Pages -

Publisher

MDPI
DOI: 10.3390/biom11060822

Keywords

preeclampsia; HMGA; immunotolerance; extravillous trophoblast; placentation

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan [19K09781]
  2. smoking research foundation [2018G024]
  3. Grants-in-Aid for Scientific Research [19K09781] Funding Source: KAKEN

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Preeclampsia is a serious disease that can be fatal for both the mother and fetus. Research suggests that poor placental formation due to remodeling failure may be one of its causes. The high-mobility group protein A may play a key role in the placental formation process, and its dysfunction may be related to the pathogenesis of preeclampsia.
Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure-derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation.

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