MiR-126 targets IL-17A to enhance proliferation and inhibit apoptosis in high-glucose-induced human retinal endothelial cells

2020 ◽  
Vol 98 (2) ◽  
pp. 277-283 ◽  
Author(s):  
Xiujuan Chen ◽  
Xuequn Yu ◽  
Xinxiang Li ◽  
Li Li ◽  
Fang Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Vision Loss ◽  
Retinal Endothelial Cells ◽  
Interleukin 17A ◽  
Novel Target ◽  
Induced Apoptosis

Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM), which results in vision loss. This study explored the role of miR-126 in high-glucose-induced human retinal endothelial cells (HRECs) and its underlying molecular mechanisms. The results showed that the expression levels of miR-126 and interleukin-17A (IL-17A) in high-glucose-induced HRECs were downregulated and upregulated, respectively. Functionally, overexpression of miR-126 promoted proliferation and suppressed apoptosis in high-glucose-induced HRECs, while IL-17A reversed the effects induced by miR-126. However, overexpression of IL-17A inhibited the proliferation and induced apoptosis, while knockdown of IL-17A accelerated the proliferation and repressed apoptosis. In addition, miR-126 repressed the expression of IL-17A, Bax, and caspase-3, while promoting the expression of survivin and phosphorylation of PI3K and AKT; restoration of IL-17A rescued these effects. Furthermore, IL-17A was identified as a target of miR-126. This indicates that miR-126 enhances proliferation and inhibits apoptosis in high-glucose-induced HRECs by activating the PI3K–AKT pathway, increasing survivin levels, and decreasing Bax and caspase-3 expression by targeting IL-17A, suggesting that miR-126 could be a novel target for preventing DR.

scholarly journals High Glucose-Induced Apoptosis Is Linked to Mitochondrial Connexin 43 Level in RRECs: Implications for Diabetic Retinopathy

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3102
Author(s):  
Aravind Sankaramoorthy ◽  
Sayon Roy
Keyword(s):  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
High Glucose ◽  
Connexin 43 ◽  
Caspase 3 ◽  
Vision Loss ◽  
Mitochondrial Morphology ◽  
Mitochondrial Fragmentation ◽  
Retinal Endothelial Cells ◽  
Induced Apoptosis

Diabetic retinopathy (DR) is one of the most common causes of vision loss and blindness among the working-age population. High glucose (HG)-induced decrease in mitochondrial connexin 43 (mtCx43) level is known to promote mitochondrial fragmentation, cytochrome c release, and apoptosis in retinal endothelial cells associated with DR. In this study, we investigated whether counteracting HG-induced decrease in mtCx43 level would preserve mitochondrial integrity and prevent apoptosis. Rat retinal endothelial cells (RRECs) were grown in normal (N; 5 mM glucose) or HG (30 mM glucose) medium for 7 days. In parallel, cells grown in HG were transfected with Cx43 plasmid, or empty vector (EV), as control. Western blot (WB) analysis showed a significant decrease in mtCx43 level concomitant with increased cleaved caspase-3, Bax, cleaved PARP, and mitochondrial fragmentation in cells grown in HG condition compared to those grown in N medium. When cells grown in HG were transfected with Cx43 plasmid, mtCx43 level was significantly increased and resulted in reduced cleaved caspase-3, Bax, cleaved PARP and preservation of mitochondrial morphology with a significant decrease in the number of TUNEL-positive cells compared to those grown in HG alone. Findings from the study indicate a novel role for mtCx43 in regulating apoptosis and that maintenance of mtCx43 level could be useful in preventing HG-induced apoptosis by reducing mitochondrial fragmentation associated with retinal vascular cell loss in DR.

scholarly journals SENP1-Mediated Desumoylation of DBC1 Inhibits Apoptosis Induced by High Glucose in Bovine Retinal Pericytes

2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
Jian Gao ◽  
Xia Chen ◽  
Qing Gu ◽  
Xiaoxiao Liu ◽  
Xun Xu
Keyword(s):  
Diabetic Retinopathy ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Characteristic Change ◽  
High Concentration ◽  
Retinal Pericytes ◽  
Specific Protease ◽  
Induced Apoptosis ◽  
Pericyte Loss

Pericyte loss is an early characteristic change in diabetic retinopathy, but its precise molecular mechanisms have not been elucidated. This study investigated the role of SENP1 in pericyte loss in diabetic retinopathy. We demonstrated that a high concentration of glucose inhibited the expression of the Sentrin/SUMO-specific protease 1 (SENP1), which resulted in an increase in DBC1 sumoylation in bovine retinal pericytes (BRPCs). Furthermore, SENP1 overexpression attenuated hyperemia-induced apoptosis of BPRCs, and SENP1 knockdown aggravated this effect. We also provide evidence that DBC1 sumoylation/desumoylation is involved in the SENP1-regulated apoptosis of BRPCs under high glucose conditions. Understanding the role of SENP1 in the pathogenesis of high glucose induced pericyte loss could help elucidate important targets for future pharmacological interventions.

scholarly journals Molecular mechanisms of estrogen receptor β-induced apoptosis and autophagy in tumors: implication for treating osteosarcoma

2019 ◽  
Vol 47 (10) ◽  
pp. 4644-4655
Author(s):  
Zheng-ming Yang ◽  
Min-fei Yang ◽  
Wei Yu ◽  
Hui-min Tao
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Critical Role ◽  
Osteosarcoma Cells ◽  
Proliferation And Metastasis ◽  
Induced Apoptosis

The estrogen receptors α (ERα) and β (ERβ) are located in the nucleus and bind to estrogen to initiate transcription of estrogen-responsive genes. In a variety of tumor cells, ERβ has been shown to be a tumor suppressor. In particular, ERβ has anti-proliferative effects in osteosarcoma cells. Additionally, ERβ has been proven to regulate the apoptosis-related molecules IAP, BAX, caspase-3, and PARP, and to act on the NF-κB/BCL-2 pathway to induce apoptosis in tumors. Moreover, ERβ can regulate the expression of the autophagy associated markers LC3-I/LC-3II and p62 and induce autophagy in tumors by inhibiting the PI3K/AKT/mTOR pathway and activating the AMPK pathway. Here, we review the molecular mechanisms by which ERβ induces apoptosis and autophagy in a variety of tumors to further delineate more specific molecular mechanisms underlying osteosarcoma tumorigenesis and pathogenesis. Considering the broad involvement of ERβ in apoptosis, autophagy, and their interaction, it is plausible that the critical role of ERβ in inhibiting the proliferation and metastasis of osteosarcoma cells is closely related to its regulation of apoptosis and autophagy.

scholarly journals High Glucose–Induced Apoptosis in Human Endothelial Cells Is Mediated by Sequential Activations of c-Jun NH 2 -Terminal Kinase and Caspase-3

Circulation ◽  
2000 ◽  
Vol 101 (22) ◽  
pp. 2618-2624 ◽  
Author(s):  
Feng M. Ho ◽  
Shing H. Liu ◽  
Chiau S. Liau ◽  
Por J. Huang ◽  
Shoei Y. Lin-Shiau
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Caspase 3 ◽  
Human Endothelial Cells ◽  
Induced Apoptosis

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.

scholarly journals Resveratrol Prevents ROS-Induced Apoptosis in High Glucose-Treated Retinal Capillary Endothelial Cells via the Activation of AMPK/Sirt1/PGC-1α Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jun Li ◽  
Songping Yu ◽  
Jia Ying ◽  
Tianyan Shi ◽  
Peipei Wang
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Caspase 3 ◽  
Small Interfering Rnas ◽  
Retinal Capillary ◽  
Capillary Endothelial Cells ◽  
Cellular Apoptosis ◽  
Induced Apoptosis ◽  
Amp Activated Protein Kinase

Resveratrol (RSV) is used as a protective therapy against diabetic retinopathy. However, the mechanism(s) underlying this protective effect has not been fully elucidated. Bovine retinal capillary endothelial cells (BRECs), an in vitro model, were used to investigate the mechanism of RSV. Our results showed that high glucose induced significant cellular apoptosis in BRECs, which was accompanied by increased intracellular levels of reactive oxygen species (ROS) and cleaved caspase-3. The glucose-induced apoptosis and ROS elevation were both inhibited by RSV. High glucose was found to decrease the levels of phosphorylated AMP-activated protein kinase (p-AMPK), which was accompanied by increased levels of Sirt1 and PGC-1α. These changes were reversed by RSV. We also demonstrated that AMPK regulates the modulations of Sirt1 and PGC-1α using specific inhibitors of AMPK and Sirt1 and small interfering RNAs of PGC-1α. In summary, the current study demonstrates that RSV is effective against high glucose-induced cellular apoptosis and its action is exerted via the inhibition of ROS/AMPK/Sirt1/PGC-1α pathway.

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