scholarly journals NLRP3 inflammasome mediates contrast media-induced acute kidney injury by regulating cell apoptosis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jianxiao Shen ◽  
Ling Wang ◽  
Na Jiang ◽  
Shan Mou ◽  
Minfang Zhang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Contrast Media ◽  
Nlrp3 Inflammasome ◽  
Cell Apoptosis ◽  
Kidney Injury

scholarly journals Overexpression of TOLLIP Protects against Acute Kidney Injury after Paraquat Intoxication through Inhibiting NLRP3 Inflammasome Activation Modulated by Toll-Like Receptor 2/4 Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Qiang Zheng ◽  
Hang Zhao ◽  
Dong Jia ◽  
Xu Han ◽  
Zhenning Liu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Nlrp3 Inflammasome ◽  
Cell Apoptosis ◽  
Kidney Injury ◽  
Inflammasome Activation ◽  
Toll Like Receptor ◽  
Nlrp3 Inflammasome Activation ◽  
Toll Like Receptor 2

Paraquat (PQ) can cause multiorgan failure including acute kidney injury (AKI). Our prior study showed that Toll-interacting protein (TOLLIP) protected against PQ-induced acute lung injury. However, the role of TOLLIP in PQ-induced AKI remains undefined. This study was aimed at understanding the role and mechanism of TOLLIP in AKI. Six-eight-week-old male Wistar rats were intraperitoneally injected with 25 mg/kg PQ to induce AKI for 24 h in vivo. HK-2 cells were treated with 300 μM PQ for 24 h to induce cellular injury in vitro or 300 μM PQ and 5 μM nuclear factor-κB (NF-κB) inhibitor BAY11-7082 for 24 h. Rats were infected with adenovirus carrying TOLLIP shRNA via tail vein injection and HK-2 cells with adenovirus carrying TOLLIP shRNA or TOLLIP 48 h before PQ exposure. Results showed that TOLLIP and Toll-like receptor 2/4 (TLR2/4) expressions were boosted in the kidney after PQ intoxication. The toxic effect of PQ on the kidney and HK-2 cells was exacerbated by TOLLIP knockdown, as evidenced by aggravated glomerulus and tubule injury, inflammatory infiltration, and cell apoptosis in the kidney and increased loss of cell viability and apoptotic cells in HK-2 cells. TOLLIP knockdown also enhanced PQ-induced NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation in vivo and in vitro and TLR2/4-NF-κB signaling in vitro, reflected by increased contents of proinflammatory cytokines and expressions of NLRP3 inflammasome-related proteins in the kidney and HK-2 cells and expressions of TLR2, TLR4, and nuclear NF-κB p65 in HK-2 cells. However, TOLLIP overexpression inhibited PQ-induced loss of cell viability, cell apoptosis, NLRP3 inflammasome activation, and TLR2/4-NF-κB signaling in vitro. Additionally, BAY11-7082 abolished TOLLIP knockdown-induced NLRP3 inflammasome activation in vitro, indicating that TOLLIP protected against NLRP3 inflammasome activation in PQ-induced AKI through inhibiting TLR2/4-NF-κB signaling. This study highlights the importance of TOLLIP in AKI after PQ intoxication.

scholarly journals NEAT1 aggravates sepsis-induced acute kidney injury by sponging miR-22-3p

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 333-342
Author(s):  
Yawei Feng ◽  
Jun Liu ◽  
Ranliang Wu ◽  
Peng Yang ◽  
Zhiqiang Ye ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Western Blot ◽  
Cell Apoptosis ◽  
Noncoding Rna ◽  
Cell Injury ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Western Blot Assay

AbstractBackground and aimAcute kidney injury (AKI) is a common complication of sepsis. Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays a vital role in various diseases, including AKI. This study aimed to investigate the function and mechanism of NEAT1 in sepsis-induced AKI.Materials and methodsA septic AKI model was established by treating HK-2 cells with lipopolysaccharide (LPS). The levels of NEAT1 and miR-22-3p were measured by quantitative real-time PCR. Cell apoptosis was assessed by flow cytometry. The levels of apoptosis-related protein and autophagy-related factors were examined by the western blot assay. An enzyme-linked immunosorbent assay was used to calculate the contents of inflammatory factors. The interaction between NEAT1 and miR-22-3p was validated by dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay. The levels of nuclear factor (NF)-κB pathway-related proteins were evaluated by the western blot assay.ResultsNEAT1 was upregulated, while miR-22-3p was downregulated in patients with sepsis and in LPS-stimulated HK-2 cells. LPS treatment triggered cell apoptosis, autophagy, and inflammatory response in HK-2 cells. NEAT1 knockdown attenuated LPS-induced cell injury. NEAT1 modulated LPS-triggered cell injury by targeting miR-22-3p. Furthermore, NEAT1 regulated the NF-κB pathway by modulating miR-22-3p.ConclusionDepletion of NEAT1 alleviated sepsis-induced AKI via regulating the miR-22-3p/NF-κB pathway.

scholarly journals Trends in contrast-induced acute kidney injury rate after percutaneous coronary interventions in coronary artery disease

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
O Mironova ◽  
OA Sivakova ◽  
VV Fomin
Keyword(s):  
Acute Kidney Injury ◽  
Contrast Media ◽  
Preventive Measures ◽  
Clinical Importance ◽  
Injury Rate ◽  
Kidney Injury ◽  
Percutaneous Coronary Interventions ◽  
Coronary Interventions ◽  
Percutaneous Coronary ◽  
Coronary Syndromes

Abstract Funding Acknowledgements Type of funding sources: None. Background. Contrast-induced acute kidney injury remains one of the dangerous complications of percutaneous coronary interventions, in spite of the evolution of contrast media and prevention strategies. Many researchers assume that this syndrome is not as frequent as it used to be and its clinical importance is overestimated. Purpose. The aim of the study was to assess the rates of contrast-induced acute kidney injury in a prospective study in patients with chronic coronary syndromes after percutaneous coronary interventions in 2012 and 2017 respectively. Methods. 1023 patients with chronic coronary syndromes and indications for the interventions with intra-arterial contrast media administration were included in the prospective open cohort study. 561 patients were enrolled in 2012 and 462 in 2017 respectively. The contrast media remained the same both in 2012 and 2017. Preventive measures included the administration of 0,9% saline 1 ml/kg/h intravenously and 0,5 kg/ml/h for the patients with heart failure before and after procedure. The primary endpoint was the development of contrast-induced acute kidney injury.  Results. The incidence of contrast-induced acute kidney injury decreased more than 3 times in 2017 than in 2012 (6% vs. 18,5%, 28 patients vs 104 patients respectively). The difference was statistically significant (p < 0,0001). The patients included in the study in 2017 were older, had higher body mass index and had more risk factors, than the ones enrolled in 2012. We organised several conferences for all the cardiologist involved in the treatment of patients undergoing percutaneous coronary intervention, as well as were printing materials describing the risk assessment and preventive measures that should be done in patients with chronic coronary syndromes before percutaneous coronary interventions (eg, stopping metformin and nephrotoxic drugs). Conclusion. The prevalence of contrast-induced acute kidney injury is decreasing not only due to the evolution of contrast media and preventive strategies, but also due to the higher level of education of all the doctors about the syndrome and its prognosis, as well as available preventive measures and treatment options.

scholarly journals Risk of acute kidney injury after contrast-enhanced computed tomography in emergency department

2020 ◽  
pp. 102490792091339
Author(s):  
Seda Dağar ◽  
Emine Emektar ◽  
Hüseyin Uzunosmanoğlu ◽  
Şeref Kerem Çorbacıoğlu ◽  
Özge Öztekin ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Emergency Department ◽  
Acute Kidney Injury ◽  
Intensive Care ◽  
Contrast Media ◽  
Kidney Injury ◽  
Intravenous Contrast ◽  
Contrast Enhanced ◽  
Enhanced Computed Tomography ◽  
Contrast Enhanced Computed Tomography

Background: Despite its risks associated with renal injury, intravenous contrast media increases diagnostic efficacy and hence the chance of early diagnosis and treatment, which leaves clinicians in a dilemma regarding its use in emergency settings. Objective: The aim of this study was to determine the risk and predictors of contrast-induced acute kidney injury following intravenous contrast media administration for computed tomography in the emergency department. Methods: All patients aged 18 years and older who had a basal creatinine measurement within the last 8 h before contrast-enhanced computed tomography and a second creatinine measurement within 48–72 h after computed tomography scan between 1 January 2015 and 31 December 2017 were included in the study. Characteristics of patients with and without contrast-induced acute kidney injury development were compared. Multivariate regression analysis was used to assess the predictors for contrast-induced acute kidney injury. Results: A total of 631 patients were included in the final statistical analysis. After contrast media administration, contrast-induced acute kidney injury developed in 4.9% ( n = 31) of the patients. When the characteristics of patients are compared according to the development of contrast-induced acute kidney injury, significant differences were detected for age, initial creatinine, initial estimated glomerular filtration rate, and all acute illness severity indicators (hypotension, anemia, hypoalbuminemia, and need for intensive care unit admission). A multivariate logistic regression analysis was performed. The need for intensive care unit admission (odds ratio: 6.413 (95% confidence interval: 1.709–24.074)) and hypotension (odds ratio: 5.575 (95% confidence interval: 1.624–19.133)) were the main factors for contrast-induced acute kidney injury development. Conclusion: Our study results revealed that hypotension, need for intensive care, and advanced age were associated with acute kidney injury in patients receiving contrast media. Therefore, we believe that to perform contrast-enhanced computed tomography in emergency department should not be decided only by checking for renal function tests and that these predictors should be taken into consideration.

miR-30e-5p regulates autophagy and apoptosis by targeting Beclin1 involved in contrast-induced acute kidney injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Xiaoqin Liu ◽  
Qingzhao Li ◽  
Lixin Sun ◽  
Limei Chen ◽  
Yue Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Cell Model ◽  
Kidney Injury ◽  
Cell Vitality ◽  
A Cell ◽  
Renal Tubular ◽  
Induced Apoptosis

Aims: This study aims to verify if miR-30e-5p targets Beclin1 (BECN1), a key regulator of autophagy, and investigate the function of miR-30e-5p and Beclin1 through mediating autophagy and apoptosis in contrast-induced acute kidney injury (CI-AKI). Methods: Human renal tubular epithelial HK-2 cells were treated with Urografin to construct a cell model of CI-AKI. Real-time reverse transcription–polymerase chain reaction was used to detect gene expression. The dual-luciferase reporting assay and endogenous validation were used to verify targeting and regulating function. The expressions of protein were detected using Western blot. Cell proliferation was detected using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Cell apoptosis was detected using terminal-deoxynucleoitidyl transferase mediated nick end labeling assay, and autophagy was detected using transmission electron microscopy. Results: HK-2 cells exposed to Urografin for 2 h induced a significant increase in miR-30e-5p. miR-30e-5p had a targeting effect on Beclin1. Moreover, Urografin exposure can enhance cell apoptosis by increasing caspase 3 gene expression and inhibiting autophagy, which was induced by decreased Beclin1 expression regulated by miR-30e-5p, thereby resulting in renal cell injury. Downregulation of miR-30e-5p or upregulation of Beclin1 restored cell vitality by promoting autophagy and suppressing apoptosis in Urografin-treated cells. Conclusions: Urografin increased the expression of miR-30e-5p in HK-2 cells and thus decreased Beclin1 levels to inhibit autophagy, but induced apoptosis, which may be the mechanism for CI-AKI.

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