Downregulation of microRNA‑106a‑5p alleviates ox‑LDL‑mediated endothelial cell injury by targeting STAT3

Hao, Ying; Xu, Rong; He, Yue; Zhang, Zhibo; Mao, Xudong; Lin, Ling; Hu, Jun

doi:10.3892/mmr.2020.11147

Cited by 25 publications

(15 citation statements)

References 51 publications

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“…miR-1 was also reported to directly target myosin light chain kinase (MLCK) in HUVECs in the study showing ox-LDL-induced miR-1 upregulation and MLCK downregulation in a time-and dose-dependent manner [378]. Interestingly, ox-LDL was shown to increase expression of miR-34a or miR-106a-5p, and decrease levels of direct regulators of TLR4 (miR-20a, miR-221-3p) along with deterioration of OxS in affected endothelium [379][380][381][382].…”

Section: Microrna In Mets-a Link With Endothelial Dysfunction and Hypmentioning

confidence: 97%

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

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Oxidative stress (OxS) is the cause and the consequence of metabolic syndrome (MetS), the incidence and economic burden of which is increasing each year. OxS triggers the dysregulation of signaling pathways associated with metabolism and epigenetics, including microRNAs, which are biomarkers of metabolic disorders. In this review, we aimed to summarize the current knowledge regarding the interplay between microRNAs and OxS in MetS and its components. We searched PubMed and Google Scholar to summarize the most relevant studies. Collected data suggested that different sources of OxS (e.g., hyperglycemia, insulin resistance (IR), hyperlipidemia, obesity, proinflammatory cytokines) change the expression of numerous microRNAs in organs involved in the regulation of glucose and lipid metabolism and endothelium. Dysregulated microRNAs either directly or indirectly affect the expression and/or activity of molecules of antioxidative signaling pathways (SIRT1, FOXOs, Keap1/Nrf2) along with effector enzymes (e.g., GPx-1, SOD1/2, HO-1), ROS producers (e.g., NOX4/5), as well as genes of numerous signaling pathways connected with inflammation, insulin sensitivity, and lipid metabolism, thus promoting the progression of metabolic imbalance. MicroRNAs appear to be important epigenetic modifiers in managing the delicate redox balance, mediating either pro- or antioxidant biological impacts. Summarizing, microRNAs may be promising therapeutic targets in ameliorating the repercussions of OxS in MetS.

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Section: Microrna In Mets-a Link With Endothelial Dysfunction and Hypmentioning

confidence: 97%

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

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“…In contrast, there were also several miRNAs previously reported to increase in the oxLDL-induced model and thus the inhibition of these molecules might help protect from endothelial injury, including the miR-106 and miR214. With the dose-dependently increasing miR-106-5p observed in the oxLDL-induced model, the caspase-3 activity and ROS levels increased and STAT3 is proved to be the participated direct indicator ( 27 ). Similarly, the increasing expression of the miR-214-3p in oxLDL-induced injury resulted in the suppression of glutathione peroxidase 4 (GPX4) and the knockdown of miR-214 can partially reduce the ROS increase and restore the decreased expression of GPX4and eNOS ( 28 ).…”

Section: Oxldl and Endothelial Cell Dysfunctionmentioning

confidence: 99%

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Jiang

Zhou

Nabavi³

et al. 2022

Front. Cardiovasc. Med.

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Atherosclerosis is an immuno-metabolic disease involving chronic inflammation, oxidative stress, epigenetics, and metabolic dysfunction. There is compelling evidence suggesting numerous modifications including the change of the size, density, and biochemical properties in the low-density lipoprotein (LDL) within the vascular wall. These modifications of LDL, in addition to LDL transcytosis and retention, contribute to the initiation, development and clinical consequences of atherosclerosis. Among different atherogenic modifications of LDL, oxidation represents a primary modification. A series of pathophysiological changes caused by oxidized LDL (oxLDL) enhance the formation of foam cells and atherosclerotic plaques. OxLDL also promotes the development of fatty streaks and atherogenesis through induction of endothelial dysfunction, formation of foam cells, monocyte chemotaxis, proliferation and migration of SMCs, and platelet activation, which culminate in plaque instability and ultimately rupture. This article provides a concise review of the formation of oxLDL, enzymes mediating LDL oxidation, and the receptors and pro-atherogenic signaling pathways of oxLDL in vascular cells. The review also explores how oxLDL functions in different stages of endothelial dysfunction and atherosclerosis. Future targeted pathways and therapies aiming at reducing LDL oxidation and/or lowering oxLDL levels and oxLDL-mediated pro-inflammatory responses are also discussed.

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“…It has been found various miRNAs are involved in the regulation of AKI development, such as miR-21, miR-19b-3p, and miR-204 (Chen et al, 2018;Pan et al, 2019;Lv et al, 2020). MicroRNA-106a-5p (miR-106a-5p) has been found to modulate cell apoptosis and proliferation and is able to attenuate ox-LDL-related endothelial cell injury (Hu et al, 2020;Ma et al, 2020). Recently, high-mobility group box 1 (HMGB1) has been identified as the crucial positive contributor to sepsis, and HMGB1 inhibition provides a higher therapeutic window (Deng et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Circular RNA TLK1 Promotes Sepsis-Associated Acute Kidney Injury by Regulating Inflammation and Oxidative Stress Through miR-106a-5p/HMGB1 Axis

Yang

2021

Front. Mol. Biosci.

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Sepsis is an inflammatory disorder and leads to severe acute kidney injury (AKI). Circular RNAs (circRNAs) have been identified as a critical type of regulatory noncoding RNAs (ncRNAs) that present the important functions in various diseases. In this study, we identified a novel circRNA circTLK1 in the regulation of sepsis-induced AKI. We observed that circTLK1 expression was elevated in the cecal ligation and puncture (CLP) rat model compared with that in the control rats. The urine levels of neutrophil gelatinase–associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) and the serum levels of creatinine (sCr) and blood urea nitrogen (BUN) were increased by the CLP treatment in the rats but were blocked by the circTLK1 shRNA. The circTLK1 shRNA reduced the CLP-induced kidney injury in the rats. The circTLK1 knockdown repressed oxidation stress, inflammation, and apoptosis in the sepsis-related AKI rat model. Moreover, lipopolysaccharide (LPS) treatment increased the production of TNF-α, IL-1β, and IL-6 in the HK-2 cells, while the circTLK1 shRNA could attenuate the enhancement in the cells. Bax and cleaved caspase-3 expression was upregulated, but Bcl-2 expression was downregulated by the LPS in the HK-2 cells, in which circTLK1 depletion reversed this effect in the cells. The depletion of circTLK1 attenuated the LPS-induced apoptosis in the HK-2 cells. CircTLK1 enhanced HMGB1 expression by sponging miR-106a-5p in the HK-2 cells, and miR-106a-5p and HMGB1 were involved in circTLK1-meidated injury of LPS-treated cells. Therefore, we concluded that circTLK1 contributed to sepsis-associated AKI by regulating inflammation and oxidative stress through the miR-106a-5p/HMGB1 axis. CircTLK1 and miR-106a-5p may be employed as the potential targets for the treatment of AKI.

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Downregulation of microRNA‑106a‑5p alleviates ox‑LDL‑mediated endothelial cell injury by targeting STAT3

Cited by 25 publications

References 51 publications

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Circular RNA TLK1 Promotes Sepsis-Associated Acute Kidney Injury by Regulating Inflammation and Oxidative Stress Through miR-106a-5p/HMGB1 Axis

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