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Decreased expression and activation of Stat3 in severe preeclampsia

Journal of Molecular Histology volume 46, pages 205–219 (2015)Cite this article

Abstract

Severe preeclampsia (PE) is a major cause of maternal mortality and morbidity worldwide. Signal transducer and activator of transcription 3 (Stat3) signal pathway can modulate various fundamental cellular processes. However, whether Stat3 plays a role in the pathogenesis of severe PE is unknown. Therefore, in this study, the expression levels of Stat3 pathway-related genes and proteins, Stat3, pStat3, IL-6, Mcl-1L, Bcl-xL, survivin, MMP-2, and MMP-9, were evaluated by immunohistochemistry (IHC), Western blot analysis and real-time PCR in the severe preeclamptic placentas. Our results showed that Stat3 and pStat3 immunoreactivity were localized in both extravillous cytotrophoblast cells and villous trophoblast cells in the placentas. As compared with normotensive pregnancies, significantly decreased expressions of Stat3 and pStat3 proteins were observed in extravillous cytotrophoblast cells, villous trophoblast cells and entire placentas in patients with severe PE. The expression levels of Stat3, IL-6, survivin and MMP-2 mRNA were significantly decreased in severe preeclamptic placentas, while Mcl-1L, Bcl-xL and MMP-9 mRNA levels were unchanged. IHC results further confirmed that there was a significant decrease of IL-6, survivin and MMP-2 proteins expression in the severe preeclamptic placentas compared with the normal specimens. These findings suggested that decreased expression and activation of the Stat3 may be caused by decreased expression of a Stat3 upstream gene, such as IL-6. Decreased Stat3 expression and activation may play an important role in the pathogenesis of PE through regulation of the transcription of the Stat3 targeted genes survivin and MMP-2 to modulate apoptosis and invasion of placental trophoblastic cells.

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Acknowledgments

This work was supported by Grants from the Science and Technology Fund for Innovative Talents of Henan Province (No. 124200510005), the Key Scientific and Technological Project of Henan Province (No. 112102310089), and the Science and Technology Fund for Innovation Leading Research Team of Zhengzhou City (No. 131PCXTD624).

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Affiliations

  1. Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfuqian Street, Zhengzhou, 450052, Henan Province, China

    Zhan Zhang & Xiaoqian Yang

  2. Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China

    Zhan Zhang, Linlin Zhang, Liting Jia, Peng Wang, Ying Shi & Junjun Gao

  3. Henan Provincial Engineering Research Center for Perinatal Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China

    Zhan Zhang, Linlin Zhang, Liting Jia & Ying Li

  4. Henan Translational Medicine Engineering Laboratory for Maternal and Children’s Health, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China

    Zhan Zhang, Linlin Zhang, Liting Jia & Ying Li

  5. Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Zhenfeng Duan

Authors
  1. Zhan Zhang
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  2. Xiaoqian Yang
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  3. Linlin Zhang
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  4. Zhenfeng Duan
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  5. Liting Jia
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  6. Peng Wang
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  7. Ying Shi
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  8. Ying Li
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  9. Junjun Gao
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Correspondence to Zhan Zhang.

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Cite this article

Zhang, Z., Yang, X., Zhang, L. et al. Decreased expression and activation of Stat3 in severe preeclampsia. J Mol Hist 46, 205–219 (2015). https://doi.org/10.1007/s10735-015-9613-8

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  • DOI: https://doi.org/10.1007/s10735-015-9613-8

Keywords

  • Severe preeclampsia
  • Stat3 signal pathway
  • Placenta
  • Apoptosis
  • Invasion