Effect of the p53-tristetraprolin-stathmin-1 pathway on trophoblasts at maternal-fetal interface

PLoS One. 2017 Jun 28;12(6):e0179852. doi: 10.1371/journal.pone.0179852. eCollection 2017.

Abstract

Problem: To reveal the effect of p53-tristetraprolin-stathmin-1 signaling on trophoblasts and recurrent spontaneous abortion (RSA).

Method of study: Stathmin-1 (STMN1), p53, and tristetraprolin (TTP) expression in paraffin-embedded villus tissue was determined using immunohistochemistry. HTR-8/SVneo cells were treated with doxorubicin to activate p53; STMN1 and TTP levels were detected by quantitative reverse transcription-PCR and western blotting. Western blotting and immunofluorescence were used to investigate STMN1 expression after TTP overexpression or knockdown in HTR-8 cells.

Results: STMN1 was downregulated and p53 was upregulated in the villus tissue from patients with RSA. Doxorubicin decreased STMN1 expression but enhanced TTP expression in HTR-8 cells. In vitro, TTP overexpression inhibited STMN1 production; TTP knockdown promoted it. TTP downregulated STMN1 expression in trophoblasts by directly binding its 3' untranslated region.

Conclusions: TTP modulates trophoblast function and interacts with STMN1 and p53, and is related to pregnancy outcomes.

MeSH terms

  • Abortion, Spontaneous / metabolism*
  • Adult
  • Blotting, Western
  • Cell Line
  • Doxorubicin / pharmacology
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Stathmin / physiology*
  • Tristetraprolin / physiology*
  • Trophoblasts
  • Tumor Suppressor Protein p53 / physiology*
  • Young Adult

Substances

  • STMN1 protein, human
  • Stathmin
  • Tristetraprolin
  • Tumor Suppressor Protein p53
  • Doxorubicin

Grants and funding

This work was supported by the National Basic Research Program of China (No. 2013CB967404), the National Natural Science Foundation of China (No. 81401274, 81401218, 81370767, 81501250 and 31671567), the Fund for Outstanding Academic Leaders in Shanghai, China (2013-049), the Shanghai Natural Science Fund Project (No. 14ZR1443800), key projects of Shanghai Municipal Health and Family Planning Commission (201640012), key support projects of Health and Family Planning Commission, Hubei Province (No. WJ2017Z002), and Shanghai Municipal Commission of Health and Family Planning Program (No. 15GWZK0701). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.