Dysregulated expression of ACTN4 contributes to endothelial cell injury via the activation of the p38-MAPK/p53 apoptosis pathway in preeclampsia

  • Jianlin Zhao
  • Wei Peng
  • Yuxin Ran
  • Huisheng Ge
  • Chen Zhang
  • Hong Zou
  • Yubin Ding
  • Hongbo QiEmail author
Original Article


Preeclampsia (PE) is a hypertensive disease associated with increased endothelial cell dysfunction caused by systemic oxidative stress. Alpha-actinin-4 (ACTN4) is a member of the α-actinin family of actin crosslinking proteins that are upregulated in several types of cancer. However, its role in PE remains unclear. In this study, we found that ACTN4 was localized in placenta vascular endothelial cells (ECs), and its expression was downregulated in primary human umbilical vein endothelial cells (HUVECs) from severe preeclamptic patients compared to that in HUVECs from normotensive pregnant women. ACTN4 expression was also decreased in normotensive HUVECs treated with H2O2. Downregulation of ACTN4 by siRNA or H2O2 treatment promoted normotensive HUVEC apoptosis and increased p38-MAPK phosphorylation along with elevated levels of p53 phosphorylation, caspase cascade proteins, and bax and repressed expression of bcl-2. Conversely, upregulation of ACTN4 in PE HUVECs significantly inhibited apoptosis and decreased p38-MAPK phosphorylation compared to that of the PE HUVEC controls. In addition, overexpression of ACTN4 in normotensive HUVECs attenuated H2O2 treatment-induced apoptosis with decreased p53 phosphorylation, caspase cascade, and bax expression levels and increased expression of bcl-2 compared to that of only H2O2 treatment. Moreover, the suppression of ACTN4 induced apoptosis, which could be blocked by the p38-MAPK inhibitor SB202190. Collectively, these results demonstrate that dysregulated ACTN4 expression may be associated with PE due to its effects on endothelial cell apoptosis via the p38-MAPK/p53 apoptosis pathway.


Preeclampsia Endothelial cell dysfunction Oxidative stress Apoptosis P38-MAPK/p53 pathway 



We would like to acknowledge support from the “111 program” of the Ministry of Education P.R.C. and the State Administration of Foreign Experts Affairs P.R.C.

Funding information

This study was funded by the National Key Research and Development Program on the research on birth defect prevention and control of reproductive health special emphasis (No. 2016YFC1000407), the National Natural Science Foundation of China (Nos. 81520108013, 81471472, 81771613, 81501286, 81601304, 81701479, 81701480, 81801482), and the Key Program of International Cooperation of the NSFC (No. 81520108013).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

13105_2019_700_MOESM1_ESM.docx (416 kb)
ESM 1 (DOCX 415 kb)


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Copyright information

© University of Navarra 2019

Authors and Affiliations

  • Jianlin Zhao
    • 1
    • 2
    • 3
  • Wei Peng
    • 1
    • 2
    • 3
  • Yuxin Ran
    • 1
    • 2
    • 3
  • Huisheng Ge
    • 1
    • 2
    • 3
  • Chen Zhang
    • 1
    • 2
    • 3
  • Hong Zou
    • 4
  • Yubin Ding
    • 3
    • 5
  • Hongbo Qi
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of ObstetricsThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
  2. 2.State Key Laboratory of Maternal and Fetal Medicine of Chongqing MunicipalityChongqing Medical UniversityChongqingChina
  3. 3.International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of EducationChongqing Medical UniversityChongqingChina
  4. 4.Department of ObstetricsUniversity-Town Hospital of Chongqing Medical UniversityChongqingChina
  5. 5.Laboratory of Reproductive Biology, School of Public Health and ManagementChongqing Medical UniversityChongqingChina

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