Identification and validation of the miRNA–mRNA regulatory network in fetoplacental arterial endothelial cells of gestational diabetes mellitus

He, Longkai; Wang, Xiaotong; Jin, Yifeng; Xu, Weipeng; Guan, Yi Fang; Wu, Jingchao; Han, Shasha; Liu, Guosheng

doi:10.1080/21655979.2021.1950279

Cited by 12 publications

(6 citation statements)

References 52 publications

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“…In line with this, except for miR-210-3p that was downregulated, all of them were upregulated by current hypoxia in fpEC. The fact that miR-210-3p, as a classical hypoxamiR, was reduced after 72 h of hypoxia is surprising, and we can only speculate that the induction of miR-210-3p by hypoxia has-as well as the cellular adaption to hypoxia in general [44]-a shorter dynamic than the time interval investigated here. We aimed to mimic chronic moderate hypoxic episodes, and thus, upregulation of miR-210-3p may have occurred before angiomiR analysis at 72 h. Interestingly, in rats, a downregulation of miR-210-3p was shown to enhance the expression of DNA repair molecules [45].…”

Section: Discussioncontrasting

confidence: 58%

Transient Hyperglycemia and Hypoxia Induce Memory Effects in AngiomiR Expression Profiles of Feto-Placental Endothelial Cells

Strutz

Baumann

Weiss

et al. 2021

IJMS

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Gestational diabetes (GDM) and preeclampsia (PE) are associated with fetal hyperglycemia, fetal hypoxia, or both. These adverse conditions may compromise fetal and placental endothelial cells. In fact, GDM and PE affect feto-placental endothelial function and also program endothelial function and cardiovascular disease risk of the offspring in the long-term. MicroRNAs are short, non-coding RNAs that regulate protein translation and fine tune biological processes. A group of microRNAs termed angiomiRs is particularly involved in the regulation of endothelial function. We hypothesized that transient hyperglycemia and hypoxia may alter angiomiR expression in feto-placental endothelial cells (fpEC). Thus, we isolated primary fpEC after normal, uncomplicated pregnancy, and induced hyperglycemia (25 mM) and hypoxia (6.5%) for 72 h, followed by reversal to normal conditions for another 72 h. Current vs. transient effects on angiomiR profiles were analyzed by RT-qPCR and subjected to miRNA pathway analyses using DIANA miRPath, MIENTURNET and miRPathDB. Both current and transient hypoxia affected angiomiR profile stronger than current and transient hyperglycemia. Both stimuli altered more angiomiRs transiently, i.e., followed by 72 h culture at control conditions. Pathway analysis revealed that hypoxia significantly altered the pathway ‘Proteoglycans in cancer’. Transient hypoxia specifically affected miRNAs related to ‘adherens junction’. Our data reveal that hyperglycemia and hypoxia induce memory effects on angiomiR expression in fpEC. Such memory effects may contribute to long-term adaption and maladaption to hyperglycemia and hypoxia.

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Section: Discussioncontrasting

confidence: 58%

Transient Hyperglycemia and Hypoxia Induce Memory Effects in AngiomiR Expression Profiles of Feto-Placental Endothelial Cells

Strutz

Baumann

Weiss

et al. 2021

IJMS

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“…The research then uncovered that miR-423-5p decrement could hinder insulin resistance and hepatic gluconeogenesis in GDM mice via suppressing biochemical index levels, enhancing insulin homeostasis, relieving pathological changes, and reducing the apoptosis rate of pancreatic cells. Overall, miRNA exerts pivotal effects on maternal hyperglycemia through the interaction with mRNA [ 38 ]. Comparatively, our study specifically investigated the mechanism of miR-423-5p on GDM progression.…”

Section: Discussionmentioning

confidence: 99%

Long-noncoding RNA HOXA transcript at the distal tip ameliorates the insulin resistance and hepatic gluconeogenesis in mice with gestational diabetes mellitus via the microRNA-423-5p/wingless-type MMTV integration site family member 7A axis

et al. 2022

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Long-noncoding RNA HOXA transcript at the distal tip (HOTTIP) has been probed to exert essential effects on diabetes progression, while its function in gestational diabetes mellitus (GDM) remains unclear. This study was committed to unravel the effects of HOTTIP on GDM progression via the microRNA (miR)-423-5p/wingless-type MMTV integration site family member 7A (WNT7A) axis. The GDM mouse model was established. HOTTIP, miR-423-5p and WNT7A levels in GDM mice were examined. The saline with dissolved various constructs altering HOTTIP, miR-423-5p and WNT7A expression was injected into GDM mice to detect the levels of GDM‐related biochemical indices, HOMA indices, liver gluconease: expression levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase), glucose transporter 2 (GLUT2) and pathological changes of pancreatic tissues, and the apoptosis rate of pancreatic cells in GDM mice. The relations among HOTTIP, miR-423-5p and WNT7A were validated. HOTTIP and WNT7A levels were decreased while miR-423-5p was elevated in GDM mice. The enriched HOTTIP or silenced miR-423-5p alleviated the levels of GDM‐relatedbiochemical indices, enhanced the insulin homeostasis, elevated GLUT2 expression and decreased G-6-pase and PEPCK expression, mitigated the pathological changes of pancreatic tissues, and hindered the apoptosis of pancreatic cells. MiR-143-5p upregulation abrogated the effects of elevated HOTTIP on repressing GDM; whereas WNT7A deletion reversed the therapeutic effects of reduced miR-423-5p. HOTTIP sponged miR-423-5p that targeted WNT7A. HOTTIP ameliorates insulin resistance and hepatic gluconeogenesis in GDM mice via the modulation of the miR-423-5p/WNT7A axis. This study affords novel therapeutic modalities for GDM treatment.

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“…Pregnant women with diabetes show changes in miRNA expression compared with healthy pregnant women, and changes in miRNA expression are also observed in the fetus and placenta. [9][10][11] A recent study identified 316 miRNAs dysregulated in the hearts of mice with streptozotocin (STZ)-induced diabetes mellitus. 12 Compared with that of healthy pregnant women, the expression of miR-21 in the serum and placenta of patients with gestational diabetes mellitus (GDM) is reduced.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of miR-21-5p rescues the inhibition of cardiomyocyte proliferation induced by high glucose through negative regulation of Rhob

Wu,

Wang,

Yang

et al. 2023

J Dev Orig Health Dis

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Increasing evidence shows that maternal hyperglycemia inhibits cardiomyocyte (CM) proliferation and promotes cell apoptosis during fetal heart development, which leads to cardiac dysplasia. Accumulating evidence suggests that the overexpression of miR-21 in CMs has a protective role in cardiac function. Therefore, we investigated whether miR-21 can rescue CM injury caused by high glucose. First, we performed biological function analysis of miR-21-5p overexpression in H9c2 cells treated with high glucose. We found that the proliferation of H9c2 cells treated with high glucose decreased significantly and was rescued after overexpression of miR-21-5p. CCK-8 and EdU incorporation assays were performed to assess cell proliferation. The cell proliferation of the miR-21-5p mimic transfection group was improved compared with that of the NC mimic group (*p < 0.05, miR-21-5p mimics vs. NC mimics) when the proliferation of H9c2 cells was reduced by high glucose (****p < 0.0001, high glucose (HG) vs. normal glucose (NG)). Then, we verified the targeted and negative regulation of miR-21-5p on Rhob using a dual-luciferase activity assay and RT-qPCR, respectively. We further demonstrated that miR-21-5p regulates Rhob to rescue the inhibition of CM proliferation induced by high glucose. The CCK-8 results showed that the cell proliferation of the siRNA-Rhob group was higher than that of the NC mimic group (***p < 0.001) and that of the cotransfection group with Up-Rhob plasmids and miR-21-5p mimics was lower than that of the miR-21-5p mimic group (*p < 0.05). Conclusion: Overexpression of miR-21-5p rescues the inhibition of high glucose-induced CM proliferation through regulation of Rhob.

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Identification and validation of the miRNA–mRNA regulatory network in fetoplacental arterial endothelial cells of gestational diabetes mellitus

Cited by 12 publications

References 52 publications

Transient Hyperglycemia and Hypoxia Induce Memory Effects in AngiomiR Expression Profiles of Feto-Placental Endothelial Cells

Transient Hyperglycemia and Hypoxia Induce Memory Effects in AngiomiR Expression Profiles of Feto-Placental Endothelial Cells

Long-noncoding RNA HOXA transcript at the distal tip ameliorates the insulin resistance and hepatic gluconeogenesis in mice with gestational diabetes mellitus via the microRNA-423-5p/wingless-type MMTV integration site family member 7A axis

Upregulation of miR-21-5p rescues the inhibition of cardiomyocyte proliferation induced by high glucose through negative regulation of Rhob

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