Thioredoxin, thioredoxin interacting protein and transducer and activator of transcription 3 in gestational diabetes
- 20 Downloads
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.
KeywordsGDMA2 TXNIP TXN SOCS3 STAT3 NFƙB-p50
Gestational diabetes mellitus
Gestational Diabetes Mellitus class A2
Thioredoxin interacting protein
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.
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
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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)
Informed consent was obtained from all individual participants included in the study prior to enrollment.
- 2.American Diabetes A (2018) Management of diabetes in pregnancy: standards of medical care in diabetes-2018. Diabetes Care 41:S137–S143Google Scholar
- 3.Pasternak Y, Aviram A, Poraz I, Hod M (2013) Maternal nutrition and offspring's adulthood NCD's: a review. J Mater Fetal Neonatal Med 26:439–444Google Scholar
- 22.American Diabetes A (2019) Classification and diagnosis of diabetes: standards of medical care in diabetes-2019. Diabetes Care 42:S13–S28Google Scholar
- 23.Zitman-Gal T, Einbinder Y, Ohana M, Katzav A, Kartawy A, Benchetrit S (2019) Effect of liraglutide on the Janus kinase/signal transducer and transcription activator (JAK/STAT) pathway in diabetic kidney disease in db/db mice and in cultured endothelial cells. J Diabetes 11:656–664PubMedGoogle Scholar
- 31.Eren E, Aykal G, Sayrac S, Erol O, Ellidag HY, Yilmaz N (2017) Relationship between thioredoxin and thioredoxin-binding protein in patients with gestational diabetes mellitus. J Matern Fetal Neonatal Med 30:164–168Google Scholar
- 35.Sato BL, Sugawara A, Ward MA, Collier AC (2014) Single blastomere removal from murine embryos is associated with activation of matrix metalloproteinases and Janus kinase/signal transducers and activators of transcription pathways of placental inflammation. Mol Hum Reprod 20:1247–1257PubMedPubMedCentralGoogle Scholar