Skip to main content

Advertisement

Log in

CREB-binding protein (CREBBP) and preeclampsia: a new promising target gene

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Preeclampsia (PE) is a major complication of pregnancy and remains a leading cause of neonatal and maternal mortality worldwide. Several studies have revealed that the incidence of preeclampsia is high in mothers who carried a fetus with Rubinstein-Taybi Syndrome due to the mutation in CREBBP. We aimed to compare the expression level of the CERBBP gene between preeclamptic and healthy placenta in our study. The expression level of CREBBP gene was evaluated in a total of one hundred placental biopsies from PE patients and healthy pregnant women after delivery using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the differential expression of CREBBP was assessed between the maternal and fetal sides of the placenta. Expression of the CREBBP gene was higher in preeclampsia patients compared with the controls (Fold change = 2.158; P = 0.018). Moreover, the gene expression was slightly higher in the fetal side of the placenta, although it was not significantly different (Fold change = 1.713, P = 0.254). Our findings show a role for CREBBP in the pathogenesis of PE. Due to the important role of CREBBP in angiogenesis and hypoxia, the gene may serve as a promising target in future studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Tsakiridis I, Arvanitaki A, Zintzaras E (2019) Assessing the reporting quality of systematic reviews of observational studies in preeclampsia. Arch Gynecol Obstet 299(3):689–694

    Article  Google Scholar 

  2. Zha W, Guan S, Liu N, Li Y, Tian Y, Chen Y et al (2020) Let-7a inhibits Bcl-xl and YAP1 expression to induce apoptosis of trophoblast cells in early-onset severe preeclampsia. Sci Total Environ 745:139919

    Article  CAS  Google Scholar 

  3. Agarwal I, Karumanchi SA (2011) Preeclampsia and the anti-angiogenic state. Pregnancy Hypertens: Int J Women’s Cardiovasc Health 1(1):17–21

    Article  Google Scholar 

  4. Gray KJ, Saxena R, Karumanchi SA (2018) Genetic predisposition to preeclampsia is conferred by fetal DNA variants near FLT1, a gene involved in the regulation of angiogenesis. Am J Obstet Gynecol 218(2):211–218

    Article  CAS  Google Scholar 

  5. Levine RJ, Maynard SE, Qian C, Lim K-H, England LJ, Yu KF et al (2004) Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 350(7):672–683

    Article  CAS  Google Scholar 

  6. Laresgoiti-Servitje E, Gomez-Lopez N (2012) The pathophysiology of preeclampsia involves altered levels of angiogenic factors promoted by hypoxia and autoantibody-mediated mechanisms. Biol Reprod. https://doi.org/10.1095/biolreprod.112.099861

    Article  PubMed  Google Scholar 

  7. Wang F, Marshall CB, Ikura M (2013) Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: structural and functional versatility in target recognition. Cell Mol Life Sci 70(21):3989–4008

    Article  CAS  Google Scholar 

  8. Jiang H, Chen S-S, Yang J, Chen J, He B, Zhu L-H et al (2012) CREB-binding protein silencing inhibits thrombin-induced endothelial progenitor cells angiogenesis. Mol Biol Rep 39(3):2773–2779

    Article  CAS  Google Scholar 

  9. van Uitert M, Moerland PD, Enquobahrie DA, Laivuori H, van der Post JA, Ris-Stalpers C et al (2015) Meta-analysis of placental transcriptome data identifies a novel molecular pathway related to preeclampsia. PLoS ONE 10(7):e0132468

    Article  Google Scholar 

  10. Ilekis JV, Reddy UM, Roberts JM (2007) Preeclampsia—a pressing problem: an executive summary of a National Institute of Child Health and Human Development workshop. Reprod Sci 14(6):508–523

    Article  CAS  Google Scholar 

  11. Roberts JM, Gammill HS (2005) Preeclampsia: recent insights. Hypertension 46(6):1243–1249

    Article  CAS  Google Scholar 

  12. Matsubara K (2017) Hypoxia in the pathogenesis of preeclampsia. Hypertens Res Pregnancy 5(2):46–51

    Article  Google Scholar 

  13. Hamilton MJ, Newbury-Ecob R, Holder-Espinasse M, Yau S, Lillis S, Hurst JA et al (2016) Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum. Clin Dysmorphol 25(4):135–145

    Article  Google Scholar 

  14. Shen J, Zhao M, Zeng Z, He W, Chen C (2020) CREBBP gene mutation in an infant with Rubinstein-Taybi syndrome. J Cent South Univ Med Sci 45(2):198–203

    Google Scholar 

  15. Yu S, Wu B, Qian Y, Zhang P (2019) Clinical exome sequencing identifies novel CREBBP variants in 18 Chinese Rubinstein-Taybi Syndrome kids with high frequency of polydactyly. Mol Genet Genom Med 7(12):e1009

    CAS  Google Scholar 

  16. English FA, Kenny LC, McCarthy FP (2015) Risk factors and effective management of preeclampsia. Integr Blood Press Control 8:7

    PubMed  PubMed Central  Google Scholar 

  17. Kleinrouweler CE, Wiegerinck MM, Ris-Stalpers C, Bossuyt PM, van der Post JA, von Dadelszen P et al (2012) Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin in the prediction of pre-eclampsia: a systematic review and meta-analysis. BJOG: Int J Obstet Gynaecol 119(7):778–787

    Article  CAS  Google Scholar 

  18. Chappell LC, Duckworth S, Seed PT, Griffin M, Myers J, Mackillop L et al (2013) Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation 128(19):2121–2131

    Article  CAS  Google Scholar 

  19. Wu D, Zhau H, Huang W, Iqbal S, Habib F, Sartor O et al (2007) cAMP-responsive element-binding protein regulates vascular endothelial growth factor expression: implication in human prostate cancer bone metastasis. Oncogene 26(35):5070–5077

    Article  CAS  Google Scholar 

  20. Mochan S, Dhingra MK, Gupta SK, Saxena S, Arora P, Yadav V et al (2019) Status of VEGF in preeclampsia and its effect on endoplasmic reticulum stress in placental trophoblast cells. Eur J Obstet Gynecol Reprod Biol: X. 4:100070

    Article  Google Scholar 

  21. Tannetta D, Sargent I (2013) Placental disease and the maternal syndrome of preeclampsia: missing links? Curr Hypertens Rep 15(6):590–599

    Article  CAS  Google Scholar 

  22. Korkes HA, De Oliveira L, Sass N, Salahuddin S, Karumanchi SA, Rajakumar A (2017) Relationship between hypoxia and downstream pathogenic pathways in preeclampsia. Hypertens Pregnancy 36(2):145–150

    Article  Google Scholar 

  23. Ziello JE, Jovin IS, Huang Y (2007) Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med 80(2):51

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Masoud GN, Li W (2015) HIF-1α pathway: role, regulation and intervention for cancer therapy. Acta Pharm Sin B 5(5):378–389

    Article  Google Scholar 

  25. Kasper LH, Boussouar F, Boyd K, Xu W, Biesen M, Rehg J et al (2005) Two transactivation mechanisms cooperate for the bulk of HIF-1-responsive gene expression. EMBO J 24(22):3846–3858

    Article  CAS  Google Scholar 

  26. Zhang Z, Wang X, Zhang L, Shi Y, Wang J, Yan H (2017) Wnt/β-catenin signaling pathway in trophoblasts and abnormal activation in preeclampsia (Review). Mol Med Rep 16(2):1007–1013

    Article  CAS  Google Scholar 

  27. Zhang Z, Li H, Zhang L, Jia L, Wang P (2013) Differential expression of β-catenin and Dickkopf-1 in the third trimester placentas from normal and preeclamptic pregnancies: a comparative study. Reprod Biol Endocrinol 11:17

    Article  Google Scholar 

  28. Zhang Z, Zhang L, Zhang L, Jia L, Wang P, Gao Y (2013) Association of Wnt2 and sFRP4 expression in the third trimester placenta in women with severe preeclampsia. Reprod Sci 20(8):981–989

    Article  CAS  Google Scholar 

  29. Li J, Sutter C, Parker DS, Blauwkamp T, Fang M, Cadigan KM (2007) CBP/p300 are bimodal regulators of Wnt signaling. EMBO J 26(9):2284–2294

    Article  CAS  Google Scholar 

  30. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A et al (2012) STRING v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41(D1):D808–D815

    Article  Google Scholar 

  31. National Collaborating Centre for Ws, Children’s H. National Institute for Health and Clinical Excellence: Guidance. Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. RCOG Press, London. Copyright © 2011, Royal College of Obstetricians and Gynaecologists; 2010

  32. Atallah A, Lecarpentier E, Goffinet F, Doret-Dion M, Gaucherand P, Tsatsaris V (2017) Aspirin for prevention of preeclampsia. Drugs 77(17):1819–1831

    Article  CAS  Google Scholar 

  33. Li D, Wang P, Yu Y, Huang B, Zhang X, Xu C et al (2018) Tumor-preventing activity of aspirin in multiple cancers based on bioinformatic analyses. PeerJ 6:e5667

    Article  Google Scholar 

  34. Wei J, Yang Y, Lu M, Lei Y, Xu L, Jiang Z et al (2018) Recent advances in the discovery of HIF-1α-p300/CBP inhibitors as anti-cancer agents. Mini Rev Med Chem 18(4):296–309

    Article  CAS  Google Scholar 

  35. Zou LJ, Xiang QP, Xue XQ, Zhang C, Li CC, Wang C et al (2019) Y08197 is a novel and selective CBP/EP300 bromodomain inhibitor for the treatment of prostate cancer. Acta Pharmacol Sin 40(11):1436–1447

    Article  CAS  Google Scholar 

  36. Gang EJ, Hsieh YT, Pham J, Zhao Y, Nguyen C, Huantes S et al (2014) Small-molecule inhibition of CBP/catenin interactions eliminates drug-resistant clones in acute lymphoblastic leukemia. Oncogene 33(17):2169–2178

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge all participants for their collaboration in this research. This study was financially supported by the “Research Department of the School of Medicine Shahid Beheshti University of Medical Sciences” (Pajoohan code: 22424).

Funding

This study was funded by the “Research Department of the School of Medicine, Shahid Beheshti University of Medical Sciences” (Grant Number: 22424).

Author information

Authors and Affiliations

Authors

Contributions

Authors participated in conception and design (HS, RP, LG, RM), clinical data collection and statistical analysis (RP, SE, MRG, GAT), performing molecular experiments (SE, GAT and MAB), and drafting the article or revising critically for important intellectual content (HS, MG and RM).

Corresponding author

Correspondence to Reza Mirfakhraie.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was in accordance with the ethical standards of the ethics committee of Shahid Beheshti University of Medical Sciences and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical approval was obtained from Shahid Beheshti University of Medical Sciences ethics committee (Code No: IR.SBMU.RETECH.REC.1399.99).

Informed consent

All subjects signed the informed consent form prior to the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sadeghi, H., Esmkhani, S., Pirjani, R. et al. CREB-binding protein (CREBBP) and preeclampsia: a new promising target gene. Mol Biol Rep 48, 2117–2122 (2021). https://doi.org/10.1007/s11033-021-06215-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06215-1

Keywords

Navigation