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Thioredoxin, thioredoxin interacting protein and transducer and activator of transcription 3 in gestational diabetes

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Abstract

To evaluate changes in the inflammatory response of thioredoxin (TXN), thioredoxin interacting protein (TXNIP), transducer and activator of transcription 3, NFƙB-p50 and STAT3 at the level of maternal serum, placenta, and umbilical cord blood of women with gestational diabetes mellitus type 2 (GDMA2) compared to normal pregnancies (NP). Thirty pregnant women (20 with GDMA2 and 10 NP) were recruited during admission for delivery. Blood samples were obtained from the parturients and umbilical cords, as well as placental tissue for mRNA and protein extraction. TXNIP mRNA expression was significantly increased in maternal serum of women with GDMA2 compared to NP women. TXNIP mRNA was significantly decreased in GDMA2 placentas and cord blood compared to NP. TXN/TXNIP mRNA ratio showed significantly high absolute values in placental and cord blood (2.39 and 1.66) respectively, compared to maternal ratio (1.084) (P < 0.001). TXN/TXNIP placenta protein ratio showed similar values between GDMA2 and NP (0.98 and 0.86; P = 0.7). STAT3 and its target protein SOCS3, as well as NFƙB-p50 mRNA expression were significantly increased in placentas of GDMA2. NFƙB-p50 mRNA expression was significantly decreased in cord blood compared to both maternal and placental mRNA expression. Pro-inflammatory changes are expressed by low mRNA TXN/TXNIP ratio in maternal blood of GDMA2 patients, but not in placental and umbilical cord blood samples. This, as well as the feedback role of SOCS3 in STAT3 pathway and NFƙB-p50 expression, may indicate that the placenta has a role in protecting the fetus from damage due to inflammatory response, which is common in diabetes.

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Abbreviations

GDM:

Gestational diabetes mellitus

GDMA2:

Gestational Diabetes Mellitus class A2

TXNIP:

Thioredoxin interacting protein

TXN:

Thioredoxin

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Acknowledgements

We thank the delivery room staff of Meir Medical Center for helping recruit women to the study. We thank Faye Schreiber for editing the manuscript and Navah Jelin for assistance with the statistical analysis. They are both employees of Meir Medical Center.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel

    Yael Pasternak & Tal Biron-Shental

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Yael Pasternak, Tal Biron-Shental, Sydney Benchetrit & Tali Zitman-Gal

  3. Nephrology Laboratory, Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israel

    Meital Ohana, Keren Cohen-Hagai, Sydney Benchetrit & Tali Zitman-Gal

Authors
  1. Yael Pasternak
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  2. Meital Ohana
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  3. Tal Biron-Shental
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  4. Keren Cohen-Hagai
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  5. Sydney Benchetrit
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  6. Tali Zitman-Gal
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Contributions

Y.P; T.B.S; K.C.H;S.B and T.Z.G conception and design of research; Y.P; M.O and T.Z.G data and blood collection; Y.P; M.O and T.Z.G performed experiments; Y.P ;M.O; K.C.H and T.Z.G analyzed data, interpreted results and prepared figures; Y.P, T.B.S; K.C.H; S.B and T.Z.G drafted manuscript; Y.P ; T.B.S ;S.B and T.Z.G edited and revised manuscript; all authors approved the final version of manuscript

Corresponding author

Correspondence to Tali Zitman-Gal.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Meir Medical Center local Ethics Committee (approval no. 0132-16-MMC)

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Informed consent was obtained from all individual participants included in the study prior to enrollment.

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Pasternak, Y., Ohana, M., Biron-Shental, T. et al. Thioredoxin, thioredoxin interacting protein and transducer and activator of transcription 3 in gestational diabetes. Mol Biol Rep 47, 1199–1206 (2020). https://doi.org/10.1007/s11033-019-05221-8

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  • DOI: https://doi.org/10.1007/s11033-019-05221-8

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