High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells

Hong, Feng; Gu, Junjie; Gou, Fang; Huang, Wei; Gao, Chenlin; Guo, Cui; Long, Yang; Zhou, Xueqin; Yang, Maojun; Liu, Shuang; Lu, Shishi; Luo, Qiaoyan; Xu, Yong

doi:10.1155/2016/6973175

Cited by 102 publications

(77 citation statements)

References 49 publications

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“…In addition to these points, stress-response pathway activation would be induced by ROS accumulation immediately, and apoptosis would be subsequently increased [32]. Simultaneously, many apoptosis stimuli, including treatment with tumour necrosis factor (TNF)-α [33] and lipopolysaccharide (LPS) [34] and growth factor withdrawal, can induce ROS generation through mitochondria [35]. In addition, antioxidants such as N-acetylcysteine, thioredoxin and MnSOD can mediate this effect and postpone apoptosis [36].…”

Section: Discussionmentioning

confidence: 99%

Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications

Sun

Wang

et al. 2019

Cells

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Background: The present study was designed to explore the underlying role of hypoxia-inducible factor 1α (HIF-1α) in reactive oxygen species (ROS) formation and apoptosis in osteosarcoma (OS) cells induced by hypoxia. Methods: In OS cells, ROS accumulated and apoptosis increased within 24 h after exposure to low HIF-1α expression levels. A co-expression analysis showed that HIF was positively correlated with Forkhead box class O1 (FoxO1) expression and negatively correlated with CYP-related genes from the National Center for Biotechnology Information's Gene Expression Omnibus (NCBI GEO) datasets. Hypoxia also considerably increased HIF-1α and FoxO1 expression. Moreover, the promoter region of FoxO1 was directly regulated by HIF-1α. We inhibited HIF-1α via siRNA and found that the ROS accumulation and apoptosis induced by hypoxia in OS cells decreased. In this study, a murine xenograft model of BALB-c nude mice was adopted to test tumour growth and measure the efficacy of 2-ME + As 2 O 3 treatment. Results: Ad interim knockdown of HIF-1α also inhibited manganese-dependent superoxide dismutase (MnSOD), catalase and sestrin 3 (Sesn3) expression in OS cells. Furthermore, hypoxia-induced ROS formation and apoptosis in OS cells were associated with CYP450 protein interference and were ablated by HIF-1α silencing via siRNA. Conclusions: Our data reveal that HIF-1α inhibits ROS accumulation by directly regulating FoxO1 in OS cells, which induces MnSOD, catalase and Sesn3 interference, thus resulting in anti-oxidation effects. The combination of an HIF-1α inhibitor (2-mercaptoethanol,2-ME) and ROS inducer (arsenous oxide, As 2 O 3 ) can prohibit proliferation and migration and promote apoptosis in MG63 cells in vitro while inhibiting tumour growth in vivo.

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Section: Discussionmentioning

confidence: 99%

Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications

Sun

Wang

et al. 2019

Cells

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“…In this study, we identified that TXNIP was a direct target of miR‐335‐3p at its 3′‐UTR mRNA by bioinformatics, which was confirmed by luciferase reporter assays, and miR‐335‐3p overexpression suppressed NPC apoptosis and TXNIP expression at mRNA and protein levels, while silencing miR‐335‐3p led to an opposite effect. TXNIP, an endogenous inhibitor of thioredoxin, mediates NLRP3 inflammasome activation in various inflammatory diseases including, but not limited to diabetic retinopathy , rheumatoid arthritis (RA) , nonalcoholic fatty liver disease (NAFLD) . In this study, we confirmed that TXNIP expression at mRNA and protein levels was increased in IDD patients as compared to patients with spinal cord injury.…”

Section: Discussionmentioning

confidence: 99%

LINC00969 promotes the degeneration of intervertebral disk by sponging miR‐335‐3p and regulating NLRP3 inflammasome activation

Hao

et al. 2018

IUBMB Life

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Long noncoding RNAs (LncRNAs) may serve as miRNA sponges to regulate the expressions of miRNA target genes. LncRNA LINC00969 has been indicated to be upregulated in intervertebral disk degeneration. However, the regulatory mechanism of LINC00969 in intervertebral disk degeneration progression remains unclear. Differently expressed LINC00969, miR‐335‐3p, and thioredoxin‐interacting protein (TXNIP) were determined in nucleus pulposus (NP) tissues and cells isolated from patients with intervertebral disk degeneration. The interaction between LINC00969, miR‐335‐3p, and TXNIP was also assessed. In this study, we demonstrated that LINC00969 was highly expressed, whereas miR‐335‐3p was aberrantly downregulated in NP tissues and cells of intervertebral disk degeneration patients. In addition, our results suggested that LINC00969 enhanced NP cell apoptosis. More importantly, LINC00969 was identified to function as a competitive endogenous RNA (ceRNA) for miR‐335‐3p to positively regulate TXNIP expression in vitro. Our study provided evidence for the cross‐talk between LINC00969, miR‐335‐3p, and TXNIP, shedding light on the therapy for intervertebral disk degeneration. © 2018 IUBMB Life, 71(5):611–618, 2019

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“…It is typically associated with persistent inflammation response due to infiltration of immune cells and cytokines [14]. Several inflammatory cytokines are activated during the process of wound healing.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 Inflammasome Expression and Signaling in Human Diabetic Wounds and in High Glucose Induced Macrophages

Zhang

Dai

et al. 2017

Journal of Diabetes Research

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Introduction. To investigate the contribution and mechanism of NLRP3 inflammasome expression in human wounds in diabetes mellitus and in high glucose induced macrophages. Methods. In the present study, we compared the expression of NLRP3 inflammasome in debridement wound tissue from diabetic and nondiabetic patients. We also examined whether high glucose induces NLRP3 inflammasome expression in cultures THP-1-derived macrophages and the influence on IL-1β expression. Results. The expressions of NLRP3, caspase1, and IL-1β, at both the mRNA and protein level, were significantly higher in wounds of diabetic patients compared with nondiabetic wounds (P < 0.05). High glucose induced a significant increase in NLRP3 inflammasome and IL-1β expression in THP-1-derived macrophages. M1 macrophage surface marker with CCR7 was significantly upregulated after high glucose stimulation. SiRNA-mediated silencing of NLRP3 expression downregulates the expression of IL-1β. Conclusion. The higher expression of NLRP3, caspase1, and secretion of IL-1β, signaling, and activation might contribute to the hyperinflammation in the human diabetic wound and in high glucose induced macrophages. It may be a novel target to treat the DM patients with chronic wound.

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High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells

Cited by 102 publications

References 49 publications

Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications

Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications

LINC00969 promotes the degeneration of intervertebral disk by sponging miR‐335‐3p and regulating NLRP3 inflammasome activation

NLRP3 Inflammasome Expression and Signaling in Human Diabetic Wounds and in High Glucose Induced Macrophages

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