Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Expression levels of urotensin II are associated with endoplasmic reticulum stress in patients with severe preeclampsia

Abstract

Hypertensive disorders in pregnancy remain a leading cause of maternal and perinatal mortality and morbidity. We aim to study urotensin II (UII) and its association with the markers of endoplasmic reticulum stress (ERS) in placentas of patients with severe preeclampsia (SPE). Thirty-three patients with hypertensive disorders in pregnancy and twenty-two healthy pregnant women designated as healthy controls were recruited. Expression levels of UII, UII receptor (GPR14) and the markers of ERS in placenta specimens of patients were performed. Plasma and urinary UII levels were measured by radioimmunoassay method. Our study showed that the plasma levels of UII in patients with hypertensive disorders during pregnancy were significantly higher than that of the healthy control group. However, the urinary levels of UII had no difference in two groups. The expression level of mRNA and protein of UII, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulation protein 78 in placentas of SPE was significantly increased. Immunohistochemical analyses show that the expression levels of UII and ERS markers were mainly located in the cytoplasm of placental trophoblastic cells. Moreover, expression level of UII mRNA and protein was positively correlated with that of the markers of ERS. The positive correlation between UII and ERS markers expression level also corresponded with the level of patient’s systolic blood pressure and proteinuria. In conclusion, we first verify that expression of UII is associated with ERS in patients with SPE. Our results indicate that UII may trigger ERS in placental trophoblastic cells in patients with preeclampsia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Gould PS, Gu M, Liao JQ, Ahmad S, Cudmore MJ, Ahmed A et al. Up regulation of urotensin II receptor in preeclampsia causes in vitro placental release of soluble vascular endothelial growth factor receptor 1 in hypoxia. Hypertension 2010; 56: 172–178.

    Article  CAS  Google Scholar 

  2. Liane LA, Loset LM, Mundal SB, Fenstad MH, Johnson MP, Eide IP . Increased endoplasmic reticulum stress in decidual tissue from pregnancies complicated by fetal growth restriction with and without pre-eclampsia. Placenta 2011; 32: 823–829.

    Article  Google Scholar 

  3. Eric AP, Dadelszen PV, Duvekot JJ, Pijnenborg R . Pre-eclampsia. Lancet 2010; 376: 631–644.

    Article  Google Scholar 

  4. Veerbeek JH, Tissot Van Patot MC, Burton GJ, Yung HW . Endoplasmic reticulum stress is induced in the human placenta during labour. Placenta 2015; 36: 88–92.

    Article  CAS  Google Scholar 

  5. Ames RS, Sarau HM, Chambers JK . Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 1999; 40: 282–286.

    Article  Google Scholar 

  6. Balat O, Aksoy F, Kutlar I, Ugur MG, Iyikosker H, Balat A et al. Increased plasma levels of Urotensin-II in preeclampsia–eclampsia: a new mediator in pathogenesis? Eur J Obstet Gynecol Reprod Biol 2005; 120: 33–38.

    Article  CAS  Google Scholar 

  7. Matsushita M, Shichiri M, Imai T, Iwashina M, Tanaka H, Takasu N et al. Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues. J Hypertens 2001; 19: 2185–2190.

    Article  CAS  Google Scholar 

  8. Cowley E, Thompson JP, Sharpe P, Waugh J, Ali N, Lambert DG . Effects of pre-eclampsia on maternal plasma, cerebrospinal fluid, and umbilical cord urotensin II concentrations: a pilot study. Br J Anaesth 2005; 95: 495–499.

    Article  CAS  Google Scholar 

  9. Jarry M, Diallo M, Lecointre C . The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte cell activity through common and distinct mechanisms: involvement in cell proliferation. Biochem J 2010; 428: 113–124.

    Article  CAS  Google Scholar 

  10. Mekahli D, Bultynck G, Parys JB, Smedt HD, Missiaen L . Endoplasmic-reticulum calcium depletion and disease. Cold Spring Harb Perspect Biol 2011; 3: 1–30.

    Article  Google Scholar 

  11. Bai Q, Zhang J, Zhang AH, Cheng LT, He L, Fan MH et al. Roles of human urotensin II in volume resistance hypertension in peritoneal dialysis patients. Ren Fail 2012; 340: 713–717.

    Article  Google Scholar 

  12. Totsune K, Takahashi K, Arihara Z, Sone M, Ito S, Murakami O . Increased plasma urotensin II level s in patients with diabetes mellitus. Clin Sci 2003; 104 (1): 1–5.

    Article  CAS  Google Scholar 

  13. Jain A, Olovsson M, Burton GJ, Yung HW . Endothelin-1 induces endoplasmic reticulum stress by activating the PLC-IP (3) pathway: implications for placental pathophysiology in preeclampsia. Am J Pathol 2012; 180: 2309–2320.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Natural Science Foundation (Grant No. 81170706 and Grant No 81341022) to A-H Zhang.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A-H Zhang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, WY., Chen, GJ., Lai, X. et al. Expression levels of urotensin II are associated with endoplasmic reticulum stress in patients with severe preeclampsia. J Hum Hypertens 30, 129–135 (2016). https://doi.org/10.1038/jhh.2015.28

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2015.28

This article is cited by

Search

Quick links