Cell and Tissue Research

, 344:551

Gadd45α as an upstream signaling molecule of p38 MAPK triggers oxidative stress-induced sFlt-1 and sEng upregulation in preeclampsia

  • Xin Luo
  • Zhen-wei Yao
  • Hong-bo Qi
  • Dan-dan Liu
  • Guo-qing Chen
  • Shuai Huang
  • Qing-shu Li
Regular Article

DOI: 10.1007/s00441-011-1164-z

Cite this article as:
Luo, X., Yao, Z., Qi, H. et al. Cell Tissue Res (2011) 344: 551. doi:10.1007/s00441-011-1164-z

Abstract

Preeclampsia (PE) is known to be associated with increased circulating levels of anti-angiogenic factors, such as soluble fms-related tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). However, the way that placental oxidative stress results in the elevation of these two factors remains enigmatic. We have observed the overexpression of growth arrest and DNA damage-inducible 45 alpha (Gadd45α) and excessive activation of p38 mitogen-activated protein kinase (MAPK) in preeclamptic placentas compared with normotensive controls, together with increased levels of sFlt-1 and sEng in maternal sera in patients with PE. Moreover, Gadd45α knockdown or p38 inhibition provides protective effects in hypoxia/reoxygenation (H/R)-exposed human umbilical vein endothelial cells (HUVECs) by suppressing oxidative stress, inhibiting apoptosis, and promoting their potential for in vitro angiogenesis. A regulatory signaling pathway in which H/R intervention causes the induction of Gadd45α leading to p38 activation and ultimately an increase in sFlt-1 and sEng secretion in HUVECs has concurrently been established. Our study opens up a promising new avenue of investigation for increasing the understanding of the origin of sFlt-1 and sEng in PE and provides novel therapeutic targets for pregnancy complications arising from placental endothelial dysfunction.

Keywords

Preeclampsia Oxidative stress Growth arrest and DNA damage-inducible 45 alpha (Gadd45α) p38 mitogen-activated protein kinase (MAPK) Soluble fms-related tyrosine kinase-1 (sFlt-1) Soluble endoglin (sEng) Human 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Xin Luo
    • 1
  • Zhen-wei Yao
    • 1
  • Hong-bo Qi
    • 1
  • Dan-dan Liu
    • 1
  • Guo-qing Chen
    • 1
  • Shuai Huang
    • 1
  • Qing-shu Li
    • 2
  1. 1.Department of Obstetrics and GynecologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingPeople’s Republic of China
  2. 2.Department of PathologyChongqing Medical UniversityChongqingPeople’s Republic of China

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