Dysregulated GLUT1 may be involved in the pathogenesis of preeclampsia by impairing decidualization

Yang, Man; Li, Hua; Rong, Miaomiao; Hong-ya, Zhang; Hou, Linlin; Zhang, Cong

doi:10.1016/j.mce.2021.111509

Cited by 18 publications

(9 citation statements)

References 52 publications

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“…One study confirmed that in mice deficient in SLC2A1, the Wnt7b-induced bone anabolic function is blocked and bone formation is affected [ 49 ]. SLC2A1 (GLUT1) is one of the targets of miR-140-5p [ 50 ], and miR-140-5p may promote the development of femoral head necrosis through the ubiquitin proteasome system [ 51 ]. This study confirmed that SLC2A1 is downregulated in SONFH tissues as did the previous literature [ 52 ], suggesting that the biological process through which miR-140-5p targets SLC2A1 may be closely related to the development of SONFH.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism

Cai

et al. 2023

Biomedicines

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Osteonecrosis of the femoral head (ONFH) is a common disabling disease. Copper has positive effects on cells that regulate bone metabolism. However, the relationship between copper metabolism (CM) and steroid-induced ONFH (SONFH) remains unclear. The GSE123568 dataset was downloaded from the Gene Expression Omnibus. The differentially expressed CM-related SONFH genes (DE-CMR-SONFHGs) were identified via differential analysis and weighted gene coexpression network analysis (WGCNA). Receiver operating characteristic (ROC) analysis was performed for the predictive accuracy of key genes. Targeting drugs and the copper death-related genes (CDRGs) relevant to key genes were investigated. The bioinformatics results were confirmed via quantitative real-time polymerase chain reaction (qRT–PCR) and Western blot (WB) analysis. Two out of 106 DE-CMR-SONFHGs were identified as key genes (PNP and SLC2A1), which had diagnostic value in distinguishing SONFH from control samples and were related to various immune cell infiltrations. Eleven PMP-targeting drugs and five SLC2A1-targeting drugs were identified. The qRT–PCR, as well as WB, results confirmed the downregulation PNP and SLC2A1 and high expression of the CDRGs DLD, PDHB, and MTF1, which are closely related to these two key genes. In conclusion, PNP and SLC2A1 were identified as key genes related to SONFH and may provide insights for SONFH treatment.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism

Cai

et al. 2023

Biomedicines

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“…GLUT1 protein expression was found to be down-regulated, and glucose transport activity was decreased in placentas from pregnancies affected by preeclampsia ( 51 ). Recently, a study showed that in addition to reduced GLUT1 in the decidua of patients with severe preeclampsia, GLUT1 deficiency may trigger aberrant glycolysis, thereby leading to poor decidualization and subsequent impaired placental development ( 52 ). Furthermore, a recent study showed that O -GlcNAcylation mediates the regulation of the water channel aquaporin 3 (AQP3) and that both elevated O -GlcNAcylation and AQP3 increase glucose uptake via GLUT1 ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy

et al. 2022

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IntroductionDuring pregnancy, arterial hypertension may impair placental function, which is critical for a healthy baby's growth. Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. However, it is unclear how protein O-GlcNAcylation affects placental function and fetal growth throughout pregnancy during hypertension.MethodsTo investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). On the 14th, 17th, and 20th DOP, rats were euthanized, fetal parameters were measured, and placentas were collected for western blot, immunohistochemical, and morphological analyses.ResultsSHR presented a higher blood pressure than the Wistar rats (p=0.001). Across all DOPs, SHR showed reduced fetal weight and an increase in small-for-gestational-age fetuses. While near-term placentas were heavier in SHR (p=0.006), placental efficiency decreased at 17 (p=0.01) and 20 DOPs (p<0.0001) in this group. Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. O-GlcNAc protein expression was lower in placentas from SHR compared with Wistar at 14, 17, and 20 DOPs. Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. Moreover, glucose transporter 1 expression was decreased in placentas from SHR in all DOPs.ConclusionsThese findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth.

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“…96,101 Another RNA-Seq study confirmed that GLUT1 was downregulated in the decidua of severe preeclampsia. 145 Therefore, dysglycolysis may impair decidualization; hinder blastocyst implantation, trophoblast invasion, and placental development; and increase the risk of preeclampsia. However, the decidua samples used in the aforementioned studies were derived from post-cesarean sections.…”

Section: Preeclampsiamentioning

confidence: 99%

Glycolysis: A fork in the path of normal and pathological pregnancy

Gou,

Zhang

2023

The FASEB Journal

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Glucose metabolism is vital to the survival of living organisms. Since the discovery of the Warburg effect in the 1920s, glycolysis has become a major research area in the field of metabolism. Glycolysis has been extensively studied in the field of cancer and is considered as a promising therapeutic target. However, research on the role of glycolysis in pregnancy is limited. Recent evidence suggests that blastocysts, trophoblasts, decidua, and tumors all acquire metabolic energy at specific stages in a highly similar manner. Glycolysis, carefully controlled throughout pregnancy, maintains a dynamic and coordinated state, so as to maintain the homeostasis of the maternal–fetal interface and ensure normal gestation. In the present review, we investigate metabolic remodeling and the selective propensity of the embryo and placenta for glycolysis. We then address dysregulated glycolysis that occurs in the cellular interactive network at the maternal–fetal interface in miscarriage, preeclampsia, fetal growth restriction, and gestational diabetes mellitus. We provide new insights into the field of maternal–fetal medicine from a metabolic perspective, thus revealing the mystery of human pregnancy.

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Dysregulated GLUT1 may be involved in the pathogenesis of preeclampsia by impairing decidualization

Cited by 18 publications

References 52 publications

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism

Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy

Glycolysis: A fork in the path of normal and pathological pregnancy

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