Identification of a novel association for the WWOX/HIF1A axis with gestational diabetes mellitus (GDM).
| Autor: | Baryla I; Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland., Pluciennik E; Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland., Kośla K; Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland., Wojcik M; Department of Structural Biology, Medical University of Lodz, Lodz, Poland., Zieleniak A; Department of Structural Biology, Medical University of Lodz, Lodz, Poland., Zurawska-Klis M; Department of Internal Diseases and Diabetology, Medical University of Lodz, Lodz, Poland., Cypryk K; Department of Internal Diseases and Diabetology, Medical University of Lodz, Lodz, Poland., Wozniak LA; Department of Structural Biology, Medical University of Lodz, Lodz, Poland., Bednarek AK; Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland. |
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| Jazyk: | angličtina |
| Zdroj: | PeerJ [PeerJ] 2021 Jan 14; Vol. 9, pp. e10604. Date of Electronic Publication: 2021 Jan 14 (Print Publication: 2021). |
| DOI: | 10.7717/peerj.10604 |
| Abstrakt: | Background: Although the WW-domain-containing oxidoreductase (WWOX)/Hypoxia-inducible factor 1 (HIF1) pathway is a well-known regulator of cellular glucose and energy metabolism in pathophysiological processes, its role in gestational diabetes mellitus (GDM), remains elusive. We undertook this study to determine the effect of WWOX/HIF1A signaling on the expression of glucose metabolism genes in GDM patients. Methods: Leukocytes were obtained from 135 pregnant women with ( n = 98) or without ( n = 37) GDM and, in turn, 3 months ( n = 8) and 1 year ( n = 12) postpartum. Quantitative RT-PCR was performed to determine gene expression profiles of the WWOX/HIF1A-related genes, including those involved in glucose transport ( SLC2A1, SLC2A4 ), glycolytic pathway ( HK2, PKM2, PFK, LDHA ), Wnt pathway ( DVL2, CTNNB1 ), and inflammatory response ( NFKB1 ). Results: GDM patients displayed a significant downregulation of WWOX with simultaneous upregulation of HIF1A which resulted in approximately six times reduction in WWOX/HIF1A ratio. As a consequence, HIF1A induced genes ( SLC2A1, HK2, PFK, PKM ) were found to be overexpressed in GDM compared to normal pregnancy and negative correlate with WWOX/HIF1A ratio. The postpartum WWOX expression was higher than during GDM, but its level was comparable to that observed in normal pregnancy. Conclusions: The obtained results suggest a significant contribution of the WWOX gene to glucose metabolism in patients with gestational diabetes. Decreased WWOX expression in GDM compared to normal pregnancy, and in particular reduction of WWOX/HIF1A ratio, indicate that WWOX modulates HIF1α activity in normal tissues as described in the tumor. The effect of HIF1α excessive activation is to increase the expression of genes encoding proteins directly involved in the glycolysis which may lead to pathological changes in glucose metabolism observed in gestational diabetes. Competing Interests: The authors declare there are no competing interests. (©2021 Baryla et al.) |
| Databáze: | MEDLINE |
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