scholarly journals Differential Expression of miR-136 in Gestational Diabetes Mellitus Mediates the High-Glucose-Induced Trophoblast Cell Injury through Targeting E2F1

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Chunxia Zhang ◽  
Li Wang ◽  
Jinfeng Chen ◽  
Fei Song ◽  
Yuzhen Guo
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cell Viability ◽  
High Glucose ◽  
Target Gene ◽  
Trophoblast Cell ◽  
Luciferase Reporter ◽  
Trophoblast Cells

Background. Gestational diabetes mellitus (GDM) seriously affects the health of mothers and infants. The high-glucose-induced inhibition in trophoblast cell viability is an important event in GDM pathogenesis. This study evaluated the expression and clinical significance of miR-136 in GDM patients, and the biological function and related mechanisms of miR-136 in the regulation of trophoblast cell proliferation were explored. Methods. The expression of miR-136 in serum and placenta of GDM patients was measured using quantitative Real-Time PCR. Trophoblast cells were stimulated with high-glucose medium to mimic the pathological changes of GDM, and the effect of miR-136 was examined by CCK-8 assay. A luciferase reporter assay was used to confirm the target gene of miR-136, and the relationship of E2F transcription factor 1 (E2F1) with miR-136 in GDM was further analyzed. Results. miR-136 expression was significantly elevated in GDM serum and tissue samples. By high-glucose treatment, trophoblast cell proliferation was inhibited and miR-136 expression was promoted. The knockdown of miR-136 could promote the proliferation of trophoblast cells exposed to high glucose, whereas the overexpression of miR-136 could suppress it. In addition, E2F1 was identified as a target gene of miR-136, which could mediate the regulatory effect of miR-136 on trophoblast cell proliferation. Conclusion. Collectively, miR-136 expression is increased in both serum and placental tissues in GDM patients, and miR-136 mediates the inhibiting effect of high glucose on trophoblast cell viability by targeting E2F1.

scholarly journals Circ-PNPT1 contributes to gestational diabetes mellitus (GDM) by regulating the function of trophoblast cells through miR-889-3p/PAK1 axis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Li Zhang ◽  
Ming Zeng ◽  
Fei Tang ◽  
Jun Chen ◽  
Dongmei Cao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cell Viability ◽  
Trophoblast Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Trophoblast Cells ◽  
Binding Interaction

Abstract Background Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. CircRNA polyribonucleotide nucleotidyltransferase 1 (circ-PNPT1) has been found to be abnormally expressed in GDM patients. However, function and mechanism of circ-PNPT1 in GDM remain largely undefined. Methods Levels of circ-PNPT1, microRNA (miR)-889-3p and PAK1 (p21 (RAC1) activated kinase 1) were detected using quantitative real-time polymerase chain reaction and Western blot assays. Cell viability, apoptosis, migration and invasion were determined using cell counting kit-8 assay, flow cytometry, transwell and wound healing assays, respectively. The binding interaction between miR-889-3p and circ-PNPT1 or PAK1 was verified using dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Exosomes were obtained from culture media by the use of commercial kits and qualified by transmission electron microscopy (TEM). Results Circ-PNPT1 was highly expressed in the placental tissues of GDM and high glucose (HG)-induced trophoblast cells. Knockdown of circ-PNPT1 reversed HG-induced arrest of trophoblast cell viability, migration, invasion and the promotion of cell apoptosis. Mechanistically, we confirmed circ-PNPT1 could promote the expression of PAK1, the target of miR-889-3p, by directly sponging miR-889-3p, and circ-PNPT1 regulated HG-induced trophoblast cell dysfunction by miR-889-3p/PAK1 axis. Further studies showed circ-PNPT1 was packaged into exosomes and could be internalized by surrounding trophoblast cells. Conclusion Circ-PNPT1 promoted HG-induced trophoblast cell biological dysfunction through miR-889-3p/PAK1 axis. Meanwhile, it could be transferred from HG-induced trophoblast cells to surrounding untreated cells via exosomes.

scholarly journals miR-520h inhibits cell survival by targeting mTOR in gestational diabetes mellitus

2021 ◽  
Author(s):  
Jie Wen ◽  
Xiaoxia Bai
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Target Gene ◽  
Cell Model ◽  
Fasting Blood Glucose ◽  
Luciferase Reporter ◽  
Maternal Glucose

Gestational diabetes mellitus (GDM) is a type of diabetes that occurs during pregnancy due to abnormal maternal glucose metabolism. This study aimed to investigate the effect of miR-520h and its potential target gene on the progression of GDM. The blood samples were taken from healthy pregnant women and GDM patients. Human villous trophoblasts HTR-8/SVNEO cells were treated with 25 mM glucose and were considered as the GDM cell model. The miR-520h level was detected using qRT-PCR in the serum and GDM cell model. The correlation analysis between fasting blood-glucose (FBG) level and miR-520h expression was analyzed. The target relationship between miR-520h and mTOR was verified using dual luciferase reporter assay. HG-induced cells were transfected with miR-520h mimic or miR-520h inhibitor and pCDNA3-mTOR vector or their NCs. Cell viability, apoptosis and mTOR expression level were detected using CCK-8, flow cytometry and western blotting, respectively. The results showed that the miR-520h serum level was up-regulated in the GDM patients’ serum and GDM cell model, and was positively correlated with FBG of GDM patients. High glucose (HG) inhibited HTR-8/SVNEO cell viability and decreased mTOR expression, while it promoted apoptosis. Then, the effects of HG on HTR-8/SVNEO cells were reversed by miR-520h inhibitor. Moreover, mTOR was identified as a target gene downstream of miR-520h. The overexpression of mTOR alleviated miR-520h mimic-induced reduction in cell viability and enhancement in cell apoptosis in the GDM cell model. In conclusion, miR-520h could inhibit cell viability and promote cell apoptosis by regulating mTOR expression in the GDM cell model. Hence, miR-520h might be a potential and important marker for the diagnosis and treatment of GDM.

scholarly journals miR-132 serves as a diagnostic biomarker in gestational diabetes mellitus and its regulatory effect on trophoblast cell viability

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xuegui Zhou ◽  
Cuiping Xiang ◽  
Xiaoxia Zheng
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cell Function ◽  
Fasting Blood Glucose ◽  
Trophoblast Cell ◽  
Operating Characteristics ◽  
Diagnostic Potential

Abstract Background Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes. Strategies that improve trophoblast cell function are important methods for GDM treatment. This study aimed to investigate the expression and diagnostic potential of microRNA-132 (miR-132) in GDM patients, and further analyzed the effects of miR-132 on HTR-8/SVneo cell proliferation. Methods Quantitative real-time PCR was applied to estimate the expression of miR-132. A receiver operating characteristics curve (ROC) analysis was performed to evaluate the diagnostic value of serum miR-132 in GDM patients. In vitro regulation of miR-132 in trophoblast cell HTR-8/SVneo was achieved by cell transfection, and the effects of miR-132 on cell proliferation were assessed using CCK-8 assay. Results Expression of miR-132 was decreased in serum and placenta tissues in GDM patients compared with the healthy women. A negative correlation was found between the serum miR-132 levels and fasting blood glucose of the GDM patients. A ROC curve shown the serum miR-132 had considerable diagnostic accuracy with an area under the curve (AUC) of 0.898. High glucose (HG) treatment induced an inhibition in HTR-8/SVneo cell proliferation and the expression of miR-132. The overexpression of miR-132 in HTR-8/SVneo cells could markedly rescued the HG - induced suppressed cell proliferation. Conclusion All the data of this study revealed the reduced expression of miR-132 in serum and placenta tissues of GDM, and serum miR-132 serves a candidate biomarker in the diagnosis of GDM. miR-132 may act a protective role against GDM via enhancing the trophoblast cell proliferation.

High Glucose Level Induces Cardiovascular Dysplasia During Early Embryo Development

2017 ◽  
Vol 127 (09) ◽  
pp. 590-597
Author(s):  
Yi-mei Jin ◽  
Shu-zhu Zhao ◽  
Zhao-long Zhang ◽  
Yao Chen ◽  
Xin Cheng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Reactive Oxygen Species ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
High Glucose ◽  
Reactive Oxygen ◽  
Early Embryo ◽  
Yolk Sac ◽  
Oxygen Species ◽  
Excess Reactive Oxygen Species

AbstractThe incidence of gestational diabetes mellitus (GDM) has increased dramatically amongst multiethnic population. However, how gestational diabetes mellitus damages the developing embryo is still unknown. In this study, we used yolk sac membrane (YSM) model to investigate angiogenesis in the developing chick embryo. We determined that in the presence of high glucose, it retarded the growth and extension of the embryonic vascular plexus and it also reduced the density of the vasculature in yolk sac membrane model. Using the same strategy, we used the chorioallantoic membrane (CAM) as a model to investigate the influence of high glucose on the vasculature. We established that high glucose inhibited development of the blood vessel plexus and the blood vessels formed had a narrower diameter than control vessels. Concurrent with the abnormal angiogenesis, we also examined how it impacted cardiogenesis. We determined the myocardium in the right ventricle and left atrium were significantly thicker than the control and also there was a reduction in glycogen content in cardiomyocytes. The high glucose also induced excess reactive oxygen species (ROS) production in the cardiomyocytes. We postulated that it was the excess reactive oxygen species that damaged the cardiomyocytes resulting in cardiac hyperplasia.

scholarly journals miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Pingping Wang ◽  
Zengfang Wang ◽  
Guojie Liu ◽  
Chengwen Jin ◽  
Quan Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Macrophage Polarization ◽  
Vital Role ◽  
Luciferase Reporter ◽  
M2 Macrophage ◽  
And Migration

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

High Glucose Suppresses Cardiomyocyte Progenitor Cell Regenerative Capacity and the Role of miR-195/EZH2 Crosstalk in Gestational Diabetes Mellitus

2021 ◽  
Vol 242 ◽  
pp. 162-163
Author(s):  
Pranav Mellacheruvu ◽  
Progyaparamita Saha ◽  
Sameer Ahmad Guru ◽  
Rachana Mishra ◽  
Sudhish Sharma ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
High Glucose ◽  
Progenitor Cell ◽  
Regenerative Capacity

scholarly journals Potential Role of Hyperglycemia in Fetoplacental Endothelial Dysfunction in Gestational Diabetes Mellitus

2016 ◽  
Vol 39 (4) ◽  
pp. 1317-1328 ◽  
Author(s):  
Jian Zhou ◽  
Xiaotian Ni ◽  
Xiaojie Huang ◽  
Julei Yao ◽  
Qizhi He ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Endothelial Dysfunction ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Umbilical Vein ◽  
Specific Inhibitor ◽  
Tube Formation ◽  
Placental Angiogenesis

Background: Gestational diabetes mellitus (GDM) is associated with structural and functional alterations in various tissues including endothelial dysfunction. The aim of this study was to explore the effects of hyperglycemia on fibroblast growth factor 2 (FGF2)- and vascular endothelial growth factor (VEGF)-stimulated placental angiogenesis and the underlying molecular signaling mechanisms. Methods: The density of fetal placental capillaries was examined using immunohistochemistry. Human umbilical vein endothelial cells (HUVECs) derived from GDM (dHUVECs) and normal healthy patients (nHUVECs) were used as cell models in this study. Cell proliferation, migration and tube formation were measured with an MTS assay, a transwell system and a matrigel assay, respectively. The activation of ERK1/2 was analyzed with Western blot. The specific inhibitor of extracellular signal-regulated kinases 1/2 (ERK1/2) PD98059 was used to elucidate the involved signaling pathway. Results: GDM did not alter the capillary density of the fetus-placenta. Both the GDM and hyperglycemic conditions inhibited the proliferation of the FGF2- but not the VEGF-stimulated HUVECs and the basal migratory capacity. Hyperglycemic condition significantly inhibited tube formation and ex vivo angiogenesis. Moreover, hyperglycemia inhibited the FGF2- but not the VEGF-induced activation of ERK1/2. PD98059 significantly inhibited the FGF2-activated ERK1/2 phosphorylation and the FGF2-stimulated cell proliferation in HUVECs. Conclusion: Both GDM and hyperglycemia may impair placental angiogenesis by reducing HUVEC proliferation, migration and tube formation. Hyperglycemia-inhibited cell proliferation stimulated by FGF2 probably contributed to the suppression of the MEK1/2/ERK1/2 pathways in the HUVECs.

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