Long noncoding RNA MALAT1 promotes high glucose-induced human endothelial cells pyroptosis by affecting NLRP3 expression through competitively binding miR-22

2019 ◽  
Vol 509 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Yaxian Song ◽  
Lixia Yang ◽  
Ruiwei Guo ◽  
Nihong Lu ◽  
Yankun Shi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Human Endothelial Cells ◽  
Nlrp3 Expression

scholarly journals Long noncoding RNA KCNQ1OT1 induces pyroptosis in diabetic corneal endothelial keratopathy

2020 ◽  
Vol 318 (2) ◽  
pp. C346-C359 ◽  
Author(s):  
Yanyan Zhang ◽  
Zhen Song ◽  
Xuran Li ◽  
Shuo Xu ◽  
Sujun Zhou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Cultured Cells ◽  
Corneal Edema ◽  
Corneal Endothelial Cells ◽  
Caspase 1

Diabetic corneal endothelial keratopathy is an intractable ocular complication characterized by corneal edema and endothelial decompensation, which seriously threaten vision. It has been suggested that diabetes is associated with pyroptosis, a type of programmed cell death via the activation of inflammation. Long noncoding RNA KCNQ1OT1 is commonly associated with various pathophysiological mechanisms of diabetic complications, including diabetic cardiomyopathy and diabetic retinopathy. However, whether KCNQ1OT1 is capable of regulating pyroptosis and participates in the pathogenesis of diabetic corneal endothelial keratopathy remains unknown. The aim of this study was to investigate the mechanisms of KCNQ1OT1 in diabetic corneal endothelial keratopathy. Here, we reveal that KCNQ1OT1 and pyroptosis can be triggered in diabetic human and rat corneal endothelium, along with the high glucose-treated corneal endothelial cells. However, miR-214 expression was substantially decreased in vivo and in experiments with cultured cells. LDH assay was also used to verify the existence of pyroptosis in high glucose-treated cells. Bioinformatics prediction and luciferase assays showed that KCNQ1OT1 may function as a competing endogenous RNA binding miR-214 to regulate the expression of caspase-1. To further analyze the KCNQ1OT1-mediated mechanism, miR-214 mimic and inhibitor were introduced into the high glucose-treated corneal endothelial cells. The results showed that upregulation of miR-214 attenuated pyroptosis; conversely, knockdown of miR-214 promoted it. In addition, KCNQ1OT1 knockdown by a small interfering RNA decreased pyroptosis factors expressions but enhanced miR-214 expression in corneal endothelial cells. To understand the signaling mechanisms underlying the prepyroptotic properties of KCNQ1OT1, si-KCNQ1OT1 was cotransfected with or without miR-214 inhibitor. The results showed that pyroptosis was repressed after silencing KCNQ1OT1 but was reversed by cotransfection with miR-214 inhibitor, suggesting that KCNQ1OT1 mediated pyroptosis induced by high glucose via targeting miR-214. Therefore, the KCNQ1OT1/miR-214/caspase-1 signaling pathway represents a new mechanism of diabetic corneal endothelial keratopathy progression, and KCNQ1OT1 could potentially be a novel therapeutic target.

Inhibition of long noncoding RNA MALAT1 suppresses high glucose-induced apoptosis and inflammation in human umbilical vein endothelial cells by suppressing the NF-κB signaling pathway

2020 ◽  
Vol 98 (6) ◽  
pp. 669-675
Author(s):  
Yu-Ping Gong ◽  
Ya-Wei Zhang ◽  
Xiao-Qing Su ◽  
Hai-Bo Gao
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Expression Levels ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Apoptosis And Inflammation

The study investigated the expression of long noncoding RNA (lncRNA) MALAT1 in high glucose (HG)-induced human vascular endothelial cells (HUVECs) and the role of MALAT1 in the apoptosis of HG-induced HUVECs. The HUVECs were cultured and induced with 25 mmol/L HG. After that, the HUVECs were transfected with MALAT1 siRNA. The expression levels of MALAT1 were detected with qPCR, whereas the expression levels of Bax, Bcl-2, cleaved-caspase-3, cleaved-caspase-9, p-65, and p-p65 were detected using Western blot. The roles of MALAT1 in cell activities, including apoptosis, were evaluated using the CCK-8 assay, TUNEL staining, and flow cytometry. The expression levels of inflammatory factors (TNF-α and IL-6) were measured using ELISA. The expression levels of MALAT1, TNF-α, and IL-6 in HUVECs were increased in the HG environment; however, when MALAT1 was silenced in the HUVECs, cell proliferation increased significantly, the expression levels of TNF-α, IL-6, Bax, cleaved-caspase-3, and cleaved-caspase-9 decreased, and the rate of apoptosis also decreased. Silencing MALAT1 inhibited the expression of p-p65 in HG-induced HUVECs. In conclusion, our study demonstrated that MALAT1 is upregulated in HG-induced HUVECs, and inhibition of MALAT1 inhibits HG-induced apoptosis and inflammation in HUVECs by suppression of the NF-κB signaling pathway.

Long noncoding RNA OIP5-AS1 overexpression promotes viability and inhibits high glucose-induced oxidative stress of cardiomyocytes by targeting microRNA-34a/SIRT1 axis in diabetic cardiomyopathy

2020 ◽  
Vol 21 ◽  
Author(s):  
Haiyun Sun ◽  
Chong Wang ◽  
Ying Zhou ◽  
Xingbo Cheng
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
H9c2 Cells ◽  
Promoting Effect

Objective: Diabetic cardiomyopathy (DCM) is an important complication of diabetes. This study was attempted to discover the effects of long noncoding RNA OIP5-AS1 (OIP5-AS1) on the viability and oxidative stress of cardiomyocyte in DCM. Methods: The expression of OIP5-AS1 and microRNA-34a (miR-34a) in DCM was detected by qRT-PCR. In vitro, DCM was simulated by high glucose (HG, 30 mM) treatment in H9c2 cells. The viability of HG (30 mM)-treated H9c2 cells was examined by MTT assay. The reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were used to evaluate the oxidative stress of HG (30 mM)-treated H9c2 cells. Dual-luciferase reporter assay was used to confirm the interactions among OIP5-AS1, miR-34a and SIRT1. Western blot was applied to analyze the protein expression of SIRT1. Results: The expression of OIP5-AS1 was down-regulated in DCM, but miR-34a was up-regulated. The functional experiment stated that OIP5-AS1 overexpression increased the viability and SOD level, while decreased the ROS and MDA levels in HG (30 mM)-treated H9c2 cells. The mechanical experiment confirmed that OIP5-AS1 and SIRT1 were both targeted by miR-34a with the complementary binding sites at 3′UTR. MiR-34a overexpression inhibited the protein expression of SIRT1. In the feedback experiments, miR-34a overexpression or SIRT1 inhibition weakened the promoting effect on viability, and mitigated the reduction effect on oxidative stress caused by OIP5-AS1 overexpression in HG (30 mM)-treated H9c2 cells. Conclusions: OIP5-AS1 overexpression enhanced viability and attenuated oxidative stress of cardiomyocyte via regulating miR-34a/SIRT1 axis in DCM, providing a new therapeutic target for DCM.

scholarly journals Cardiac pathologies in mouse loss of imprinting models are due to misexpression of H19 long noncoding RNA

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ki-Sun Park ◽  
Beenish Rahat ◽  
Hyung Chul Lee ◽  
Zu-Xi Yu ◽  
Jacob Noeker ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ventricular Function ◽  
Mouse Models ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Relative Importance ◽  
Maternal Loss ◽  
Loss Of Imprinting

Maternal loss of imprinting (LOI) at the H19/IGF2 locus results in biallelic IGF2 and reduced H19 expression and is associated with Beckwith-Wiedemann syndrome (BWS). We use mouse models for LOI to understand the relative importance of Igf2 and H19 mis-expression in BWS phenotypes. Here we focus on cardiovascular phenotypes and show that neonatal cardiomegaly is exclusively dependent on increased Igf2. Circulating IGF2 binds cardiomyocyte receptors to hyperactivate mTOR signaling, resulting in cellular hyperplasia and hypertrophy. These Igf2-dependent phenotypes are transient: cardiac size returns to normal once Igf2 expression is suppressed postnatally. However, reduced H19 expression is sufficient to cause progressive heart pathologies including fibrosis and reduced ventricular function. In the heart, H19 expression is primarily in endothelial cells (ECs) and regulates EC differentiation both, in vivo and in vitro. Finally, we establish novel mouse models to show that cardiac phenotypes depend on H19 lncRNA interactions with Mirlet7 microRNAs.

High Glucose Prolongs Cell-Cycle Traversal of Cultured Human Endothelial Cells

Diabetes ◽  
1987 ◽  
Vol 36 (11) ◽  
pp. 1261-1267 ◽  
Author(s):  
M. Lorenzi ◽  
J. A. Nordberg ◽  
S. Toledo
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
High Glucose ◽  
Human Endothelial Cells
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