MicroRNA-146a-5p Mediates High Glucose-Induced Endothelial Inflammation via Targeting Interleukin-1 Receptor-Associated Kinase 1 Expression

Lo, Wan-Yu; Peng, Ching‐Tien; Wang, Huang-Joe

doi:10.3389/fphys.2017.00551

Cited by 45 publications

(40 citation statements)

References 42 publications

(51 reference statements)

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“…miR‐874 can inhibit TNF‐α‐induced remodeling in human fetal airway smooth muscle cells via targeting STAT3 (Sun et al, ). In addition, miR‐874 is significantly downregulated in HG‐stimulated human aortic endothelial cells (HAEC) (Lo, Peng, & Wang, ). Here, in our studies, we verified the downregulation of miR‐874 in DN rats.…”

Section: Discussionmentioning

confidence: 99%

“…miR-874 can inhibit TNF-α-induced remodeling in human fetal airway smooth muscle cells via targeting STAT3 (Sun et al, 2018). In addition, miR-874 is significantly downregulated in HG-stimulated human aortic endothelial cells (HAEC) (Lo, Peng, & Wang, 2017 (Yu, Bo, Villani, Spencer, & Fu, 2016). Besides, TLR4 can link inflammation and fibrosis in chronic kidney diseases (Lepenies et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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MiR‐874 alleviates renal injury and inflammatory response in diabetic nephropathy through targeting toll‐like receptor‐4

Yao

Zha

Gao

et al. 2018

Journal Cellular Physiology

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Diabetic nephropathy (DN) is a kind of diabetic complication with capillary damage, and its pathogenesis remains obscure. Recently, microRNAs have been identified as diagnostic biomarkers in various diseases including DN. Toll-like receptor 4 (TLR4) contributes to inflammation, and it has been implicated in diabetes pathophysiology. This study was designed to investigate the role of miR-874 and TLR4 in a streptozotocin (STZ)-induced DN rat model and glucose-induced mouse podocyte model. In the current study, we reported that miR-874 was markedly downregulated in DN rats and glucose-induced mouse podocytes compared with the corresponding control groups with the activation of TLR4. In addition, we observed that overexpression of miR-874 was able to alleviate renal injury in DN rats. The cell counting kit (CCK-8) assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay demonstrated that glucose simulation significantly inhibited podocyte proliferation and induced cell apoptosis, which can be reversed by miR-874 mimics significantly. Notably, miR-874 overexpression dramatically attenuated the inflammatory response, indicated by the decreased levels of interleukin-6, L-1β, and tumor necrosis factor α (TNF-α). Finally, the binding correlation between miR-874 and TLR4 was confirmed by carrying out dual-luciferase reporter assay in our study. It was found that overexpression of miR-874 depressed TLR4 levels in podocytes. These findings implied for the first time that the overexpression of miR-874 repressed glucose-triggered podocyte injury through targeting TLR4 and suggested that miR-874/TLR4 axis might represent a pathological mechanism of DN.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MiR‐874 alleviates renal injury and inflammatory response in diabetic nephropathy through targeting toll‐like receptor‐4

Yao

Zha

Gao

et al. 2018

Journal Cellular Physiology

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“…In mice with T2DM, miR-146a mimics significantly ameliorated peripheral neuropathy, principally by suppressing the expression of hyperglycemia-induced proinflammatory genes ( 50 ). Moreover, miR-146a is reportedly involved in high-glucose-induced endothelial inflammation, which suggests that it may be a novel therapeutic target for diabetic vascular disease ( 25 ). Overexpression of miR-146a inhibits osteogenesis by MSCs ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…Increasing studies suggested that miR-146a exerted anti-oxidative stress effect in various pathological processes in diabetic complications ( 25 – 27 ). Wang et al reported that miR-146a decreases high glucose induced ROS generation in endothelial cells ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Exosomes Derived From Mesenchymal Stromal Cells Pretreated With Advanced Glycation End Product-Bovine Serum Albumin Inhibit Calcification of Vascular Smooth Muscle Cells

Wang

Zhu

et al. 2018

Front. Endocrinol.

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Background: The osteogenic differentiation of vascular smooth muscle cell (VSMCs) is important for the development of vascular calcification (VC), particularly in diabetes. Exosomes derived from Mesenchymal Stromal Cells (MSCs) are effective against cardiovascular diseases, yet their role in VC remains unclear. Advanced glycation end products (AGEs) inhibit bone marrow stromal cell osteogenesis by targeting osteogenesis-associated genes. Thus, we investigated the role of exosomes derived from MSCs pretreated with AGEs-BSA in VC and its potential mechanisms.Methods: Primary VSMCs and MSCs were isolated from the aorta and bone marrow of Sprague-Dawley rats, respectively. VSMCs were cultured with AGEs-BSA to induce osteogenic differentiation. Exosomes were harvested from MSCs by ultracentrifugation. MSCs and VSMCs were cocultured in Transwells, and exosomes were added to VSMC culture medium to assess their effects on osteogenic differentiation. Double luciferase reporter assay was applied to confirm that miR-146a directly targets the 3' UTR of the thioredoxin-interacting protein (TXNIP) gene.Results: Pretreatment of VSMCs with AGEs-BSA increased the expression of thioredoxin-interacting protein (TXNIP) by inhibiting that of miR-146a, resulting in enhanced ROS production and VSMC calcification. By contrast, the expression of miR-146a in MSCs was increased by AGEs-BSA treatment. Thus, miR-146a was transferred from AGEs-BSA-pretreated or miR-146a-transfected MSCs to VSMCs via exosomes. After coculture with miR-146a-containing exosomes, the AGEs-BSA-mediated increase in VSMC calcification was diminished, accompanied by decreased TXNIP expression and ROS production. Furthermore, TXNIP overexpression counteracted the anti-calcification effects of MSC-derived miR-146a-containing exosomes. In addition, TXNIP was identified as a target gene of miR-146a, and the results of double luciferase reporter assay confirmed that TXNIP was the direct target gene of miR-146a.Conclusions: Exosomes secreted by MSCs pretreated with AGEs-BSA contained a high level of miR-146a, which was transferred to VSMCs and inhibited AGEs-BSA-induced calcification in a TXNIP-dependent manner. Thus, miR-146a-containing exosomes may be a potential therapeutic target for VC.

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“…In adhesion experiments, THP-1 cells were labeled with calcein acetoxymethyl ester (Calcein-AM; Molecular Probes, Eugene, OR, USA) as previously described (Lo et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Identification of Basic Fibroblast Growth Factor as the Dominant Protector of Laminar Shear Medium from the Modified Shear Device in Tumor Necrosis Factor-α Induced Endothelial Dysfunction

2018

Front. Physiol.

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Background and Aims: Endothelial dysfunction is a hallmark of cardiovascular diseases. The straight region of an artery is protected from atherosclerosis via its laminar blood flow and high shear stress. This study investigated the cytoprotective effects of a new laminar shear medium (LSM) derived from a modified cone-and-plate shear device and identified basic fibroblast growth factor (bFGF) secreted by human aortic endothelial cells (HAECs) as the dominant protective factor in the LSM.Methods: Based on a modified cone-and-plate shear device system, HAECs were exposed to laminar shear (15 dynes/cm2) and static control for 24 h to produce a new supernatant LSM and static medium (SM). Evaluation of the protective effects of LSM and SM on endothelial dysfunction induced by tumor necrosis factor (TNF)-α (10 ng/mL), which leads to production of reactive oxygen species (ROS), inflammatory monocyte adhesion, and tissue factor activity. ROS induction-, inflammation-, and thrombosis-related genes and protein expression were evaluated by quantitative-PCR and western blotting. To identify the cytokines that played a key role in the cytoprotective action of the LSM, we used cytokine antibody arrays, selected an abundant marker cytokine, bFGF, and validated the different cytoprotective effects of recombinant bFGF (rbFGF) and neutralization by monoclonal antibody (rbFGF+Ab) co-treatment. Aortic and lung tissues from different groups of C57BL/6J mice were examined by immunohistochemistry. SB203580 (specific inhibitor of p38) and BIX02189 (specific inhibitor of MEK5) were used to identify bFGF as the main cytoprotective factor acting via p38/MAPK and MEK5-KLF2 pathways.Results: Compared with traditional LSM, the new LSM not only significantly decreased TNF-α-induced intracellular adhesion molecule 1 and plasminogen activator inhibitor type 1 gene expression, but also significantly increased heme oxygenase 1 gene expression. The new LSM and bFGF attenuated TNF-α-induced ROS induction, inflammation, and tissue factor activity and inhibited the inflammatory- and thrombosis-related gene/protein overexpression both in vitro and in vivo. Mechanistically, the cytoprotective action of bFGF was mediated via the p38/MAPK and MEK5-KLF2 pathways.Conclusion: bFGF was identified as the critical factor mediating the cytoprotective effects of LSM derived from the modified laminar shear system.

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MicroRNA-146a-5p Mediates High Glucose-Induced Endothelial Inflammation via Targeting Interleukin-1 Receptor-Associated Kinase 1 Expression

Cited by 45 publications

References 42 publications

MiR‐874 alleviates renal injury and inflammatory response in diabetic nephropathy through targeting toll‐like receptor‐4

MiR‐874 alleviates renal injury and inflammatory response in diabetic nephropathy through targeting toll‐like receptor‐4

Exosomes Derived From Mesenchymal Stromal Cells Pretreated With Advanced Glycation End Product-Bovine Serum Albumin Inhibit Calcification of Vascular Smooth Muscle Cells

Identification of Basic Fibroblast Growth Factor as the Dominant Protector of Laminar Shear Medium from the Modified Shear Device in Tumor Necrosis Factor-α Induced Endothelial Dysfunction

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