Circ_0091702 relieves lipopolysaccharide (LPS)-induced cell injury by regulating the miR-182/PDE7A axis in sepsis

2021 ◽  
Author(s):  
Xinliang Zhang ◽  
Shimin Dong
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Circular Rna ◽  
Suppressive Effect ◽  
Important Regulator ◽  
Apoptosis And Inflammation ◽  
Hk2 Cells

Abstract Circular RNA (circRNA) plays an important role in the progression of sepsis. Circ_0091702 has been found to be an important regulator of sepsis progression, so its role and mechanism in sepsis progression deserve to be further explored. LPS could suppress cell viability, while enhance cell apoptosis and inflammation to induce cell injury. Circ_0091702 was downregulated in LPS-induced HK2 cells, and its overexpression alleviated LPS-induced cell injury. MiR-182 could be sponged by circ_0091702. Moreover, miR-182 inhibitor could relieve LPS-induced cell injury, and its overexpression also reversed the inhibition of circ_0091702 on LPS-induced cell injury. PDE7A was a target of miR-182, and its expression was reduced in LPS-induced HK2 cells. Additionally, silencing of PDE7A reversed the suppressive effect of circ_0091702 on LPS-induced cell injury. Our data suggested that circ_0091702 sponged miR-182 to regulate PDE7A, thereby alleviating LPS-induced cell injury in sepsis.

scholarly journals Endoplasmic reticulum stress regulates cell injury in lipopolysaccharide-induced nerve cells

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094976
Author(s):  
Min Li ◽  
Ying Zhang ◽  
Jixing Wang
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Viability ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Cell Injury ◽  
Cell Counting ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Stress Markers

Objective Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, and excessive endoplasmic reticulum (ER) stress is closely correlated with the cell injury caused by sepsis. This study aimed to analyze the possible role of ER stress in SAE cell models. Methods PC12 and MES23.5 cells were treated with increasing concentrations of lipopolysaccharides (LPS). The Cell Counting Kit-8 assay was used to detect cell viability and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to assess cell apoptosis. In addition, the protein expression levels of ER stress markers [GRP78, CHOP, inositol-requiring enzyme 1 (IRE1), and PKR-like ER kinase (PERK)] and apoptosis-related proteins (Bax, Bcl-2, caspase-3, and cleaved caspase-3) were analyzed using western blotting. Results LPS treatment activated ER stress markers in both the PC12 and MES23.5 cells. The overexpression of GRP78 significantly reduced cell viability and enhanced cell apoptosis in a time-dependent manner. An ER stress inhibitor, 4-PBA, significantly enhanced cell viability and inhibited the cell apoptosis induced by LPS. Therefore, an enhanced unfolded protein response (UPR) and UPR suppression may regulate cell apoptosis. Conclusions UPR was shown to be involved in regulating LPS-induced neuron injury. UPR could be a potential therapeutic target in SAE.

scholarly journals Anthocyanin attenuates oxygen-glucose deprivation/reperfusion-induced apoptosis of PC12 cells via inactivation of ASK1/JNK/p38 signaling pathway

2021 ◽  
Vol 18 (10) ◽  
pp. 2037-2043
Author(s):  
Hong Zhu ◽  
Dan Ren ◽  
Lan Xiao ◽  
Ting Zhang ◽  
Ruomeng Li ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Induced Apoptosis

Purpose: To investigate whether the cytoprotective effect of anthocyanin (Anc) on oxygen-glucose deprivation/reperfusion (OGD/R)-induced cell injury is related to apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK)/p38 signaling pathway. Methods: PC12 cells were pre-treated with various concentrations of Anc (10, 50, and 100 μg/mL) in OGD/R-induced cell injury model. The 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) assay was used to assess cell viability. Cell apoptosis was measured by lactic acid dehydrogenase (LDH) release assay and flow cytometry. Western blot was employed to determine the protein expressions of BCL-2, BAX, caspase-3, p-ASK1 (Thr845), p-JNK, and p-p38. Results: The results indicate that Anc increased the viability of PC12 cells after OGD/R exposure (p < 0.05), and also efficiently rescued OGD/R-induced apoptosis (p < 0.05). Mechanistic studies showed that these protective roles of Anc are related to the inhibition of ASK1/JNK/p38 signaling pathway. Conclusion: The results indicate Anc protects against OGD/R-induced cell injury by enhancing cell viability and inhibiting cell apoptosis. The underlying mechanism of action is partly via inactivation of ASK1/JNK/p38 signaling pathway. Thus, Anc has promise as a potential natural agent to prevent and treat cerebral ischemia-reperfusion injury.

Inhibition of TRAF1 protects renal tubular epithelial cells against hypoxia/reoxygenation injury

2021 ◽  
Keyword(s):  
Cell Viability ◽  
Western Blotting ◽  
Mtt Assay ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Kidney Injury ◽  
Control Group ◽  
Injury Model ◽  
Hk2 Cells ◽  
Hypoxia Reoxygenation

Background and objective: This study aimed to explore the expression of TRAF1 in vitro kidney injury model, and the function mechanism of TRAF1 in the model growth and apoptosis. Methods: After transfecting HK2 cells with short hair RNA (shRNA), shTRAF1 gene silencing model was established. The cells were divided into shRNA group and shNC group. For kidney injury model, we used hypoxia/reoxygenation to establish H/R cell lines. MTT assay was used to determine cell viability. PI/FITC staining was used to determine cell apoptosis. The genes expressions were determined by RT-qPCR and western blotting, respectively. The concentration of MDA, SOD, iNOS and LDH was determined by ELISA. Results: The results of RT-qPCR and western blotting assay revealed that TRAF1 upregulated expression in AKI model cells. The results of MTT assay revealed that shRNA group exhibited significantly higher cell viability and lower cell apoptosis compared with the control group in H/R HK2 cells. In addition, TRAF1 downregulated expression inhibits oxidative stress response in H/R treated HK2 cell. Mechanically, TRAF1 deficiency protects HK2 cell via inhibiting p38-MAPK pathway. Conclusions: Our study suggests that TRAF1 could be a target in kidney injury treatment.

scholarly journals SOCS1 Regulates Apoptosis and Inflammation by Inhibiting IL-4 Signaling in IL-1β-Stimulated Human Osteoarthritic Chondrocytes

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Qiang He ◽  
Caihong Sun ◽  
Wei Lei ◽  
Jianbing Ma
Keyword(s):  
Cell Viability ◽  
Therapeutic Target ◽  
Cell Apoptosis ◽  
Inflammatory Factors ◽  
Cytokine Signaling ◽  
Potential Therapeutic Target ◽  
Osteoarthritic Chondrocytes ◽  
Total Knee ◽  
Apoptosis And Inflammation ◽  
Regulatory Functions

Recently, Suppressor of Cytokine Signaling 1 (SOCS1) was identified as a potential therapeutic target for osteoarthritis (OA) treatment. However, the mechanisms and signaling pathways of SOCS1 in the regulation of OA development are unclear. The purpose of the current study was to investigate whether interleukin- (IL-) 4 was involved in regulatory mechanism of SOCS1 in human osteoarthritic chondrocytes. First, IL-1βwas used to stimulate human osteoarthritic chondrocytes isolated from the articular cartilage of OA patients undergoing total knee replacement. The protein and mRNA expression levels of SOCS1 were upregulated in IL-1β-stimulated human osteoarthritic chondrocytes compared with control cells. The knockdown of SOCS1 increased cell viability and inhibited cell apoptosis. It was also found that IL-4 expression was increased by SOCS1 silencing. Additionally, knockdown of IL-4 reduced cell viability and increased cell apoptosis of osteoarthritic chondrocytes transfected with SOCS1 siRNA. Moreover, the decreased expression of inflammatory factors induced by SOCS1 was enhanced by IL-4 knockdown. In conclusion, IL-4 signaling plays a crucial role in the regulatory functions of SOCS1 in apoptosis and inflammation in human osteoarthritic chondrocytes. These findings provide a potential therapeutic target for the clinical treatment of OA.

scholarly journals LncRNA PFAL suppresses TNF-α-induced inflammation by upregulating miR-18a in WI-38 cells

2021 ◽  
Vol 19 (12) ◽  
pp. 2513-2520
Author(s):  
Yichun Xie ◽  
Hongqun Wang
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Inflammatory Diseases ◽  
Jnk Pathway ◽  
Inflammatory Injury ◽  
Mortality And Morbidity ◽  
Injury Model ◽  
Tnf Α

Purpose: Pneumonia is a serious respiratory disease among children with high mortality and morbidity all over the world. Long non-coding RNAs have been proven to play a vital role in many inflammatory diseases including pneumonia. In the present study, the protective impact of lncRNA PFAL on cell viability, cell apoptosis and secretion of inflammatory cytokines, as well as the underlying molecular mechanism in TNF-α-induced inflammatory injury model of pneumonia were investigated.Methods: WI-38 cell line was treated with 20 ng/ml TNF-α to establish an inflammatory injury model of pneumonia. LncRNA PFAL or miR-18a was up- or down-regulated in the WI-38 cells by transfection procedure. Cell viability was assessed using CCK-8 assay, while the rate of cell apoptosis was measured by utilizing flow cytometry. The mRNA expression levels of lncRNA PFAL, miR-18a, apoptosis-related and JNK pathway genes were determined with RT-qPCR. Moreover, the production of inflammatory cytokines such as IL-6 and MCP-1 were detected by using Western blot analysis.Results: The results indicated that cell viability was significantly (P<0.05) reduced, while the rate of cell apoptosis was increased in the TNF-α-induced WI-38 cells. Also, TNF-α treatment enhanced the expression of inflammatory cytokines that included IL-6 and MCP-1 in WI-38 cells. Overexpression of PFAL suppressed the injury induced by TNF-α and miR-18a was positively regulated by PFAL. Moreover, the inhibition of miR-18a weakens the effect of PFAL overexpression in TNF-α-induced cell injury. Furthermore, PFAL and miR-18a were involved in the regulation of JNK pathway.Conclusion: Overexpression of PFAL suppresses TNF-α-induced WI-38 cell injury by up-regulating miR-18a via the inactivation of JNK signaling pathway. Keywords: Inflammation, JNK pathway, miR-18a, PFAL, Pneumonia, TNF-α

scholarly journals Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 581-590
Author(s):  
Xiaoning Han ◽  
Zhiyong Yuan ◽  
Yajun Jing ◽  
Weigui Zhou ◽  
Yunbo Sun ◽  
...  
Keyword(s):  
Cell Injury ◽  
Cell Damage ◽  
Underlying Mechanism ◽  
Disease Treatment ◽  
Lncrna Transcript ◽  
Non Coding Rna ◽  
Promising Target ◽  
Important Regulator ◽  
Apoptosis And Inflammation ◽  
Long Non Coding Rna

Abstract Sepsis is a common and lethal syndrome. Long non-coding RNA (lncRNA) transcript predicting survival in AKI (TapSAKI) has recently been found to serve as an important regulator in sepsis. However, the underlying mechanism of TapSAKI in sepsis pathogenesis remains largely unknown. Our data demonstrated that lipopolysaccharide (LPS)-induced HK-2 cell injury by weakening cell viability and enhancing cell apoptosis and inflammation. TapSAKI was upregulated and miR-205 was downregulated in LPS-induced HK-2 cells. TapSAKI knockdown or miR-205 overexpression alleviated LPS-induced cytotoxicity in HK-2 cells. TapSAKI sequestered miR-205 via acting as a miR-205 sponge. Moreover, the mitigating effect of TapSAKI silencing on LPS-induced HK-2 cell injury was mediated by miR-205. Additionally, the interferon regulatory factor 3 (IRF3) signaling was involved in the regulation of the TapSAKI/miR-205 axis on LPS-induced HK-2 cell damage. Our current study suggested that TapSAKI silencing relieved LPS-induced injury in HK-2 cells at least in part by sponging miR-205 and regulating the IRF3 signaling pathway, highlighting a novel understanding for sepsis pathogenesis and a promising target for this disease treatment.

scholarly journals Astragaloside IV Attenuates Lipopolysaccharides-Induced Pulmonary Epithelial Cell Injury through Inhibiting Autophagy

Pharmacology ◽  
2019 ◽  
Vol 105 (1-2) ◽  
pp. 90-101
Author(s):  
Biwang Liu ◽  
Huan Zhao ◽  
Yonghui Wang ◽  
Huizhong Zhang ◽  
Yanmiao Ma
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Cell Model ◽  
Beclin 1 ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Astragaloside Iv ◽  
Tnf Α ◽  
Therapeutic Function

Background: Astragaloside IV has shown its promising effect on acute respiratory distress syndrome (ARDS). Objectives: We aim to explore whether astragaloside IV is effective for ARDS treatment in a lipopolysaccharides (LPS)-induced cell model and whether autophagy is involved in the therapeutic function of astragaloside IV. Methods: MLE-12 cells were induced by LPS to construct an ARDS model in vitro. Cell viability was estimated by cell counting kit-8 and cell apoptosis by flow cytometry. Lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured by enzyme-linked immunosorbent assay kit. The expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, zonula occludens (ZO)-1, Beclin-1 and autophagy-related (atg) 5 mRNA was evaluated by quantitative PCR, and the expression of ZO-1, microtubule-associated proteins 1A/1B light chain 3B (LC3B) I and, LC3B II protein by Western blot. Results: LPS effectively inhibited cell viability and LC3B I expression and enhanced LC3B II, Beclin-1 and atg5 expressions in MLE-12 cells. In LPS-induced ARDS cell model, astragaloside IV up-regulated cell viability, SOD activity and ZO-1 and LC3B I expressions but down-regulated cell apoptosis, TNF-α, IL-6, LC3B II, Beclin-1 and atg5 expressions and LDH and MDA levels. 3-methyladenine promoted cell viability and ZO-1 expression, down-regulated Beclin-1 and atg5 expression, while Rapamycin (Rap) had an opposite effect. Astragaloside IV suppressed cell viability and ZO-1 expression after the Rap treatment. Conclusions: Astragaloside IV might suppress autophagy initiation directly or indirectly through suppressing the oxidative stress and inflammatory response, which further enhances the cell viability and tight junction and reduces apoptosis in LPS-stimulated pulmonary endothelial ARDS cell model, thus exerting its therapeutic function in ARDS.

scholarly journals MicroRNA-194 Regulates Lipopolysaccharide-Induced Cell Viability by Inactivation of Nuclear Factor-κ B Pathway

2017 ◽  
Vol 43 (6) ◽  
pp. 2470-2478 ◽  
Author(s):  
Fei  Xie ◽  
Lei Yang ◽  
Lili Han ◽  
Bin Yue
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Transfection Efficiency ◽  
Human Fibroblasts ◽  
Control Group ◽  
Nuclear Factor ◽  
Effective Administration ◽  
Protein Expressions ◽  
Underlying Mechanisms

The present study explored the functional role of microRNA (miR)-194 in lipopolysaccharide (LPS) induced lung cell injury, along with the underlying mechanisms and to reveal the potential role in infantile pneumonia. Human fibroblasts WI38 cells were transfected with miR-194 mimic or miR-194 inhibitor, and the transfection efficiency was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, the cells were treated with or without LPS, and then cell viability, cell apoptosis and mRNA and protein expressions of key proteins of nuclear factor kappa B (NF-κB) pathway including inhibitor of NF-κB (IκB) α, p-65, and B-cell CLL/lymphoma (Bcl) 3 were analyzed. Results showed that overexpression and suppression of miR-194 was effective. Administration of LPS significantly decreased the cell viability and statistically promoted the percentages of apoptotic cells and increased the mRNA and protein expressions of p-65 and Bcl-3 but downregulated IκBα compared to the control group (P < 0.05 or P < 0.01). LPS in combination with miR-194 suppression further enhanced the effects of LPS on cell viability and cell apoptosis compared to the LPS group (P < 0.05). In contrast, LPS in combination with miR-194 overexpression observably reversed the effects of LPS on cell viability, cell apoptosis and mRNA and protein expressions of the key proteins (P < 0.05 or P < 0.01). In conclusion, miR-194 increases the LPS-induced the inhibition of cell viability and increasing of the cell apoptosis by inhibition of NF-κB pathway in WI38 cells. MiR-194 might be a potential targeted therapy for treatment of infantile pneumonia.

microRNA-218 Inhibits Lipopolysaccharide-Induced Bronchial Epithelial Cell Injury by Targeting E2F2

2020 ◽  
Vol 10 (8) ◽  
pp. 1161-1169
Author(s):  
Min Gong ◽  
Zhongmei Mao ◽  
Jinni Chen ◽  
Xin Ye ◽  
Xiaobing Zhou
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cell ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Bronchial Epithelial Cell ◽  
Stress Injury ◽  
Bronchial Epithelial ◽  
Oxidative Stress Injury ◽  
And Oxidative Stress

Acute bronchopneumonia is a common hospitalization disease in children and serious acute bronchopneumonia will lead to death of children. MicroRNAs (miRNAs) have been thought to be related to inflammation in many diseases. The present study aimed to investigate the relation between miR218 and E2F2 and the effect of miR-218 overexpression and E2F2 inhibition on the improvement of inflammation in LPS-induced bronchial epithelial cell. BEAS-2B cells were induced by LPS for 0, 6, 12, 24 and 48 h which the cell viability was analyzed by CCK-8 assay. The expression of miR-218 in LPS-induced bronchial epithelial cell and cell transfection was detected by RT-qPCR analysis. The levels of TNF-α, IL-1α, and IL-6 in BEAS2B cells were detected using commercially-available ELISA kits. The levels of ROS, MDA, SOD and LDH were detected by ROS assay kit and oxidative stress assay kit. The cell apoptosis was analyzed by flow cytometry analysis and DAPI and hochest staining. As a result, miR-218 was decreased in LPS-induced bronchial epithelial cell. With the time of LPS treatment extends, the cell viability was decreased. Overexpression of miR-218 reduced the expression of inflammatory cytokines and oxidative stress injury in LPS-induced BEAS2B cells. Overexpression of miR-218 reduced apoptosis of LPS-induced BEAS2B cells. E2F2 was demonstrated be a target of miR-218 which miR-218 overexpression could inhibit the expression of E2F2. E2F2 inhibition could reverse the inflammatory and oxidative stress injury of LPS-induced BEAS2B cells caused by miR-218 inhibition. E2F2 inhibition could reverse the apoptosis of LPS-induced BEAS2B cells caused by miR-218 inhibition. In addition, E2F2 inhibition could reverse the expression of p-STAT1, cleaved-caspase3 and cleaved-caspase9 in LPS-induced BEAS2B cells caused by miR-218 inhibition. In conclusion, this study indicated that miR-218 overexpression and E2F2 inhibition can alleviate the inflammation in LPS-induced bronchial epithelial cell, thereby decreasing the oxidative stress and cell apoptosis.

Geniposide alleviates lipopolysaccharide (LPS)-induced inflammation by downregulation of miR-27a in rat pancreatic acinar cell AR42J

2019 ◽  
Vol 400 (8) ◽  
pp. 1059-1068 ◽  
Author(s):  
Xiaofen Zhang ◽  
Taishan Gao ◽  
Yanhua Wang
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Control Cell ◽  
Cell Counting ◽  
Pancreatic Acinar Cells ◽  
Protective Effects ◽  
Qrt Pcr ◽  
Ar42j Cells

Abstract Pancreatitis is a disease caused by inflammation of pancreatic acinar cells. Geniposide (GEN) possesses anti-inflammation activities. Hence, we investigated the effects of GEN on lipopolysaccharide (LPS)-stimulated AR42J cells. AR42J cells were stimulated by LPS and then treated with GEN and/or transfected with miR-27a mimic or negative control. Cell viability and cell apoptosis were detected using the Cell Counting Kit-8 and flow cytometry, respectively. All related proteins were measured by Western blot. The expression of miR-27a was detected by quantitative real time-polymerase chain reaction (qRT-PCR). Moreover, the expression of inflammatory cytokines interleukin-6 (IL-6) and monocyte chemoattractant protein (MCP)-1 was analyzed by qRT-PCR and Western blot. LPS significantly decreased cell viability, and enhanced cell apoptosis and IL-6, MCP-1 expression. Then GEN administration alleviated inflammatory injury by increasing cell viability, while reducing apoptosis, and IL-6 and MCP-1 expression. GEN downregulated miR-27a expression which was induced by LPS. Transfection with miR-27a mimic partially eliminated the protective effects of GEN. The phosphorylation of JNK and c-Jun was downregulated by GEN while upregulated by miR-27a overexpression. GEN alleviates LPS-induced AR42J cell injury as evidenced by promoting cell growth, and upregulation of IL-6 and MCP-1. This process might be modulated by down-regulating miR-27a and inactivation of JNK pathway.

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