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Observation of increased levels of autophagy-related genes and proteins in women with preeclampsia: a clinical study

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Abstract

Background

Preeclampsia is a type of pregnancy-related disease that is not fully understood underlying mechanisms of it till now. Reported results from autophagy-related studies in PE show some controversial roles of this mechanism in PE development and progression. In this study, we aimed to evaluate the autophagy process in preeclampsia women.

Materials and methods

Peripheral blood was taken from 50 preeclampsia women and 50 healthy pregnant women. After PBMC isolation, Total RNA and total protein were extracted from PBMCs to cDNA synthesis and real-time PCR and western blotting, respectively. Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes were evaluated using real-time PCR. Atg5, beclin1, LC3B, and FOXO1 expression at the protein level was evaluated by the western blot technique.

Results

Real-time PCR results showed an increased expression of Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes in PE patients compared to the healthy pregnant women and also in LOPE patients in comparison with EOPE cases. Western blotting results revealed higher expression of Atg5, beclin1, LC3B, and FOXO1 proteins in PE women compared to healthy pregnant group and in LOPE patients in comparison with EOPE cases. Our findings revealed a positive correlation between proteinuria and protein levels of Atg5, beclin1, LC3B, and FOXO1 in LOPE patients.

Conclusion

Our investigation showed an elevated activation of autophagy in PE women in comparison with healthy pregnant women which is in controversy with some other studies. More targeted and comprehensive studies regarding the relationship of autophagy in pre-eclamptic women are needed.

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Data Availability

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request privately.

References

  1. Sibai B, Dekker G, Kupferminc M (2005) Pre-eclampsia The Lancet, 365(9461): p. 785–799

  2. Granger JP et al (2001) Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction. Hypertension 38(3):718–722

    Article  CAS  PubMed  Google Scholar 

  3. Harmon AC et al (2016) The role of inflammation in the pathology of preeclampsia. Clin Sci 130(6):409–419

    Article  CAS  Google Scholar 

  4. LaMarca B (2010) The role of immune activation in contributing to vascular dysfunction and the pathophysiology of hypertension during preeclampsia. Minerva Ginecol 62(2):105

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Mizushima N (2007) Autophagy: process and function. Genes Dev 21(22):2861–2873

    Article  CAS  PubMed  Google Scholar 

  6. Rubinsztein DC, Mariño G, Kroemer G (2011) Autophagy and aging Cell 146(5):682–695

    CAS  Google Scholar 

  7. Glick D, Barth S, Macleod KF (2010) Autophagy: cellular and molecular mechanisms. J Pathol 221(1):3–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yue J et al (2015) Wheat homologs of yeast ATG6 function in autophagy and are implicated in powdery mildew immunity. BMC Plant Biol 15(1):1–15

    Article  CAS  Google Scholar 

  9. Cao Y, Klionsky DJ (2007) Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res 17(10):839–849

    Article  CAS  PubMed  Google Scholar 

  10. Nakashima A et al (2019) Current understanding of autophagy in pregnancy. Int J Mol Sci 20(9):2342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gu S et al (2022) Esomeprazole inhibits hypoxia/endothelial dysfunction–induced autophagy in preeclampsia. Cell Tissue Res 388(1):181–194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nakashima A et al (2017) Autophagy regulation in preeclampsia: pros and cons. J Reprod Immunol 123:17–23

    Article  CAS  PubMed  Google Scholar 

  13. Cornelius DC, Wallace K (2020) Autophagy in preeclampsia: a new target? EBioMedicine ,57

  14. Nakashima A et al (2020) Evidence for lysosomal biogenesis proteome defect and impaired autophagy in preeclampsia. Autophagy 16(10):1771–1785

    Article  CAS  PubMed  Google Scholar 

  15. Zangbar M-SS et al (2016) Antisperm protein targets in azoospermia men. J Hum Reproductive Sci 9(1):47

    Article  CAS  Google Scholar 

  16. Amaral LM et al (2017) Pathophysiology and current clinical management of preeclampsia. Curr Hypertens Rep 19(8):1–6

    Article  CAS  Google Scholar 

  17. Gong J-S, Kim GJ (2014) The role of autophagy in the placenta as a regulator of cell death. Clin experimental reproductive Med 41(3):97

    Article  Google Scholar 

  18. Li C et al (2022) Placenta autophagy is closely associated with preeclampsia.Aging,14

  19. Saha S et al (2018) Autophagy in health and disease: a comprehensive review. Biomed Pharmacother 104:485–495

    Article  CAS  PubMed  Google Scholar 

  20. Zhao H et al (2020) The inhibition of protein kinase c β contributes to the pathogenesis of preeclampsia by activating autophagy. EBioMedicine 56:102813

    Article  PubMed  PubMed Central  Google Scholar 

  21. Anvari F et al (2015) Investigating the association of IL-17A and IL-17F with susceptibility to pre-eclampsia in iranian women.

  22. Soltani-Zangbar MS et al (2018) Angiotensin type 2 receptor gene polymorphisms and susceptibility to preeclampsia. J Reprod infertility 19(2):95

    Google Scholar 

  23. Zolfaghari MA et al (2021) A new approach to the preeclampsia puzzle; MicroRNA-326 in CD4 + lymphocytes might be as a potential suspect. J Reprod Immunol 145:103317

    Article  CAS  PubMed  Google Scholar 

  24. Kamrani A et al (2022) TIGIT and CD155 as Immune-Modulator receptor and ligand on CD4 + T cells in Preeclampsia Patients. Immunol Investig 51(4):1023–1038

    Article  CAS  Google Scholar 

  25. Yousefzadeh Y et al (2022) Evaluation of CD39, CD73, HIF-1α, and their related miRNAs expression in decidua of preeclampsia cases compared to healthy pregnant women. Mol Biol Rep 49(11):10183–10193

    Article  CAS  PubMed  Google Scholar 

  26. Pourakbari R et al (2022) Preeclampsia-Derived Exosomes Imbalance the Activity of Th17 and Treg in PBMCs from Healthy Pregnant Women Reproductive Sciences, : p. 1–12

  27. Madadi S et al (2022) Expression level of immune checkpoint inhibitory factors in preeclampsia. Hum Immunol 83(8–9):628–636

    Article  CAS  PubMed  Google Scholar 

  28. Liang XH et al (1998) Protection against fatal Sindbis virus encephalitis by beclin, a novel bcl-2-interacting protein. J Virol 72(11):8586–8596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Takacs-Vellai K et al (2005) Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans. Curr Biol 15(16):1513–1517

    Article  CAS  PubMed  Google Scholar 

  30. Pollard RT et al (2009) Southern Ocean deep-water carbon export enhanced by natural iron fertilization. Nature 457(7229):577–580

    Article  CAS  PubMed  Google Scholar 

  31. Hung T-H et al (2012) Increased autophagy in placentas of intrauterine growth-restricted pregnancies. PLoS ONE 7(7):e40957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Oh S-Y et al (2008) Autophagy-related proteins, LC3 and Beclin-1, in placentas from pregnancies complicated by preeclampsia. Reproductive Sci 15(9):912–920

    Article  CAS  Google Scholar 

  33. Kalkat M et al (2013) Placental autophagy regulation by the BOK-MCL1 rheostat. Autophagy 9(12):2140–2153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jiang N et al (2022) Epigenetic dysregulation of ASPP2 accelerates trophoblasts autophagy of placentas in preeclampsia through Beclin-1

  35. Oh S-y et al (2020) Autophagy regulates trophoblast invasion by targeting NF-κB activity. Sci Rep 10(1):1–10

    Article  Google Scholar 

  36. Ying X et al (2022) Hypoxic trophoblasts secreted exosomes promote autophagy through TINCR to impair angiogenesis and drive preeclampsia

  37. Cai H et al (2018) Low expression of MFN2 is associated with early unexplained miscarriage by regulating autophagy of trophoblast cells. Placenta 70:34–40

    Article  CAS  PubMed  Google Scholar 

  38. Aoki A et al (2018) Trophoblast-specific conditional Atg7 knockout mice develop gestational hypertension. Am J Pathol 188(11):2474–2486

    Article  CAS  PubMed  Google Scholar 

  39. Pan Y-J et al (2018) Expression of urotensin II is associated with placental autophagy in patients with severe preeclampsia. J Hum Hypertens 32(11):759–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wang X et al (2014) Acylglycerol kinase promotes cell proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. Mol Cancer 13(1):1–12

    Article  Google Scholar 

  41. Pramanik KC et al (2014) CBP-Mediated FOXO-1 Acetylation inhibits pancreatic Tumor Growth by Targeting SirTAcetylation of FOXO-1 by Capsaicin causes apoptosis. Mol Cancer Ther 13(3):687–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Medema RH et al (2000) AFX-like Forkhead transcription factors mediate cell-cycle regulation by ras and PKB through p27kip1. Nature 404(6779):782–787

    Article  CAS  PubMed  Google Scholar 

  43. Yang J-Y, Xia W, Hu MCT (2006) Ionizing radiation activates expression of FOXO3a, Fas ligand, and Bim, and induces cell apoptosis. Int J Oncol 29(3):643–648

    PubMed  Google Scholar 

  44. Furukawa-Hibi Y et al (2002) FOXO forkhead transcription factors induce G2-M checkpoint in response to oxidative stress. J Biol Chem 277(30):26729–26732

    Article  CAS  PubMed  Google Scholar 

  45. Chen C-P et al (2018) Oxidative stress reduces trophoblast FOXO1 and integrin β3 expression that inhibits cell motility. Free Radic Biol Med 124:189–198

    Article  CAS  PubMed  Google Scholar 

  46. Cho H-J et al (2019) Microgravity inhibits decidualization via decreasing akt activity and FOXO3a expression in human endometrial stromal cells. Sci Rep 9(1):1–11

    Article  Google Scholar 

  47. Fan W et al (2022) Upregulation of METTL14 contributes to trophoblast dysfunction by elevating FOXO3a expression in an m6A-dependent manner. Placenta,

  48. Liu G, Yang X, Li T (2020) Foxo4-dri alleviates age-related testosterone secretion insufficiency via targeting senescent leydig cells in aged mice. Fertil Steril 114(3):e362–e363

    Article  Google Scholar 

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Acknowledgments

This work has been done as part of Ph.D. thesis for Mr. Khudhair Rashid Khudhair Alzubaidi. This study was supported by University of Tabriz, Tabriz, Iran (Grant no: 52/422097/1). Authors would like to acknowledge Department of Immunology at Tabriz University of Medical Sciences (Iran) for their great help.

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Authors and Affiliations

  1. Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran

    Khudhair Rashid Khudhair Alzubaidi & Majid Mahdavi

  2. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

    Majid Mahdavi

  3. Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Sanam Dolati

  4. Department of Immunology, Faculty of Medicine, Medical School, Tabriz University of Medical Sciences, Tabriz, 5166614766, IR, Iran

    Mehdi Yousefi

Authors
  1. Khudhair Rashid Khudhair Alzubaidi
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  2. Majid Mahdavi
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  3. Sanam Dolati
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  4. Mehdi Yousefi
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Contributions

Study Design: Mehdi Yousefi.

Data Collection: Khudhair Rashid Khudhair Alzubaidi.

Statistical Analysis: Sanam Dolati.

Data Interpretation: Mehdi Yousefi and Majid Mahdavi.

Manuscript Preparation: Khudhair Rashid Khudhair Alzubaidi.

Literature Search: Sanam Dolati.

Funds Collection: Majid Mahdavi.

Corresponding authors

Correspondence to Majid Mahdavi or Mehdi Yousefi.

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Conflict of Interest

Authors declare no conflict of interests.

Ethics approval and consent to participate

The current study was approved by the Research Ethics Committee of Tabriz University (IR.TABRIZU.REC.1401.031). Written informed consent was obtained from all participants prior any sampling and the whole procedure of the study was fully explained.

Compliance with ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from the all participants included in the study.

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Alzubaidi, K.R.K., Mahdavi, M., Dolati, S. et al. Observation of increased levels of autophagy-related genes and proteins in women with preeclampsia: a clinical study. Mol Biol Rep 50, 4831–4840 (2023). https://doi.org/10.1007/s11033-023-08385-6

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  • DOI: https://doi.org/10.1007/s11033-023-08385-6

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