Neferine inhibits LPS-ATP-induced endothelial cell pyroptosis via regulation of ROS/NLRP3/Caspase-1 signaling pathway

2019 ◽  
Vol 68 (9) ◽  
pp. 727-738 ◽  
Author(s):  
Yang-Shuo Tang ◽  
Yan-Hua Zhao ◽  
Yong Zhong ◽  
Xiao-Zhao Li ◽  
Jia-Xi Pu ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Signaling Pathway ◽  
Caspase 1

scholarly journals MicroRNA-495 Ameliorates Cardiac Microvascular Endothelial Cell Injury and Inflammatory Reaction by Suppressing the NLRP3 Inflammasome Signaling Pathway

2018 ◽  
Vol 49 (2) ◽  
pp. 798-815 ◽  
Author(s):  
Tao  Zhou ◽  
Dao-Kang Xiang ◽  
Sui-Ning Li ◽  
Lie-Hong Yang ◽  
Lu-Fang Gao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Signaling Pathway ◽  
Inflammatory Reaction ◽  
Nlrp3 Inflammasome ◽  
Microvascular Endothelial Cell ◽  
Protein Levels ◽  
Caspase 1 ◽  
Tnf Α ◽  
Cardiac Microvascular Endothelial Cell

Background/Aims: In recent years, microRNA-495 (miR-495) has been reported to be a tumor-suppressor miR that is down-modulated in cancers. However, its potential mechanism remains unknown. Therefore, this study aimed to demonstrate the role of miR-495 in cardiac microvascular endothelial cell (CMEC) injury and inflammatory reaction by mediating the pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway. Methods: Overall, 40 mice were assigned into myocardial ischemia/reperfusion injury (MIR) and sham groups. After model establishment, the levels of troponin T (TnT), troponin I (TnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase isoenzyme MB (CK-MB), myoglobin (MYO), tumor necrosis factor-alpha (TNF-α), and interleukin 1beta (IL-1β) were detected by Enzyme-Linked Immunosorbent Assay (ELISA). Apoptosis was evaluated using Terminal deoxy (d)-UTP nick end labeling (TUNEL) staining, the level of NLRP3 protein was determined by immunohistochemical assay, and miR-495 was detected by in situ hybridization (ISH). The infarct size was determined using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The expression of miR-495 and the mRNA and protein levels of NLRP3, TNF-α, IL-1β, IL-18 and caspase-1 were evaluated by RT-qPCR and western blot analysis. After transfection, the cells were treated with a miR-495 mimic, a miR-495 inhibitor, or siNLRP3. Cell proliferation was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cell cycle and apoptosis by flow cytometry. Results: Mice with myocardial I/R injury had elevated levels of TnT, TnI, NT-proBNP, CK-MB, MYO, TNF-α and IL-1β; enhanced cell apoptosis; increased expression of NLRP3, TNF-α, IL-1β, IL-18 and caspase-1; and decreased miR-495 expression. MiR-495 was confirmed to target NLRP3. Moreover, miR-495 reduced the mRNA and protein levels of NLRP3, TNF-α, IL-1β, IL-18 and caspase-1, inhibited cell apoptosis and decreased cells at the G0/G1 phase while improving cell proliferation and increasing cells at the S phase. However, the effects of NLRP4 were proved to be reciprocal. Conclusion: In conclusion, the current study indicated that miR-495 improved CMEC injury and inflammation by suppressing the NLRP3 inflammasome signaling pathway.

scholarly journals Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

2017 ◽  
Vol 43 (4) ◽  
pp. 1346-1358 ◽  
Author(s):  
Wei-Qiang Huang ◽  
Peng Wei ◽  
Ri-Qi Lin ◽  
Feng Huang
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Endothelial Cell ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lumen Formation ◽  
Caspase 1 ◽  
Mrna And Protein Expression

Background/Aims: This study aimed to identify the role of microRNA-22 (miR-22) in endothelial cell (EC) injury in coronary heart disease (CHD) by targeting NLRP3 through the inflammasome signaling pathway. Methods: A total of 24 healthy male Sprague-Dawley (SD) rats were divided into normal and atherosclerosis groups. The atherosclerosis rats were assigned into blank, negative control (NC), miR-22 mimic, miR-22 inhibitor and miR-22 inhibitor + siNLRP3 groups. A luciferase reporter gene assay was used to detect the relationship between miR-22 and NLRP3. MiR-22 expression as well as NLRP3 and caspase-1 mRNA and protein expression were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The activity and apoptosis of coronary arterial endothelial cells (CAECs) were determined by MTT and Hoechst 33258. CAEC lumen formation was detected by a lumen formation assay. An enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β, IL-6, IL-10 and IL-18 levels. Results: The results indicated that the atherosclerosis group significantly decreased miR-22 expression but increased NLRP3 and caspase-1 mRNA and protein expression. The cell survival rate was significantly increased in the miR-22 mimic group and significantly reduced in the miR-22 inhibitor group. The miR-22 mimic group displayed a lower apoptosis rate and more cells with obvious lumen walls and numerous tubular structures, while cells in the miR-22 inhibitor group were unable to form lumen walls and had a scattered distribution compared to the blank group. The ELISA showed that IL-1β, IL-6 and IL-18 levels were markedly decreased, while IL-10 was clearly increased in the miR-22 mimic group. In contrast, in the miR-22 inhibitor group, IL-1β, IL-6 and IL-18 levels were significantly increased, and IL-10 levels were decreased. Conclusion: Our findings indicated that miR-22 could lower the levels of pro-inflammatory cytokines by inhibiting the NLRP3 inflammasome pathway, which suppresses CAEC apoptosis and protects CAECs in rats with CHD.

Th17/IL-17 induces endothelial cell senescence via activation of NF-κB/p53/Rb signaling pathway

2021 ◽  
Author(s):  
Liang Zhang ◽  
Manli Liu ◽  
Wenhua Liu ◽  
Chaojie Hu ◽  
Hongqi Li ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Signaling Pathway ◽  
Cell Senescence

Shear stress regulates endothelial cell function through SRB1-eNOS signaling pathway

2016 ◽  
Vol 34 (5) ◽  
pp. 308-313 ◽  
Author(s):  
Ying Zhang ◽  
Bin Liao ◽  
Miaoling Li ◽  
Min Cheng ◽  
Yong Fu ◽  
...  
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Signaling Pathway ◽  
Cell Function ◽  
Endothelial Cell Function

Electroacupuncture inhibits the corneal ROS/TXNIP/NLRP3 signaling pathway in a rat model of dry eye syndrome

2021 ◽  
pp. 096452842110392
Author(s):  
Yanting Yang ◽  
Dan Zhang ◽  
Lijie Wu ◽  
Ji Zhang ◽  
Danyan Wu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Dry Eye ◽  
Clinical Symptoms ◽  
Dry Eye Syndrome ◽  
Receptor Protein ◽  
Sprague Dawley ◽  
Corneal Injury ◽  
Caspase 1 ◽  
Des Model

Background: Electroacupuncture (EA) treatment has been found to ameliorate clinical symptoms in patients with dry eye, but its mechanisms are still not entirely clear. Objective: To study the regulation of EA on ocular surface function and the corneal reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/Nod-like receptor protein 3 (NLRP3) inflammatory signaling pathway in dry eye syndrome (DES) model rats. Methods: Male Sprague-Dawley (SD) rats were randomly divided into five groups: Normal, Model, Model + EA, Model + NAC (N-actetylcysteine) and Model + NS (normal saline). The DES model was developed by subcutaneous injection of scopolamine hydrobromide with exposure to an air draft in the latter four groups. After intervention, the Schirmer I test (SIT), tear film break-up time (BUT) and ROS content were measured, the histopathological changes of corneal tissues were observed, and the mRNA and protein expression levels of TXNIP, NLRP3, apoptosis-associated Speck-like protein containing CARD (ASC), caspase-1, interleukin (IL)-1β and IL-18 were detected. Results: Compared with the Model group, the SIT and BUT increased significantly in the Model + EA group after intervention (p < 0.05), and the corneal injury was improved. Corneal ROS content declined in both Model + EA and Model + NAC groups (p < 0.05), and mRNA expression of TXNIP, NLRP3, ASC and caspase-1 also decreased (p < 0.01). Corneal protein expression of TXNIP, NLRP3, IL-1β and IL-18 decreased significantly in the Model + EA group (p < 0.01). Conclusion: Inhibiting the ROS/TXNIP/NLRP3 signaling pathway may be the mechanism underlying the role of EA in improving corneal injury in DES model rats.

Sign in / Sign up

Export Citation Format

Share Document