TRIM40 inhibits IgA1-induced proliferation of glomerular mesangial cells by inactivating NLRP3 inflammasome through ubiquitination

2021 ◽  
Vol 140 ◽  
pp. 225-232
Author(s):  
Jiaojiao Shen ◽  
Qing Wu ◽  
Tingyu Liang ◽  
Jian Zhang ◽  
Jiayuan Bai ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells

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

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Hong Feng ◽  
Junling Gu ◽  
Fang Gou ◽  
Wei Huang ◽  
Chenlin Gao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Mesangial Cells ◽  
Central Component ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Interacting Protein

While inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resulting in cleavage of procaspase-1 and activation of cytokines IL-1β, IL-18, and IL-33, ultimately triggering an inflammatory cascade reaction. This study observed the expression of NLRP3 inflammasome signaling stimulated by high glucose, lipopolysaccharide, and reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine in glomerular mesangial cells, aiming to elucidate the mechanism by which the NLRP3 inflammasome signaling pathway may contribute to diabetic nephropathy. We found that the expression of thioredoxin-interacting protein (TXNIP), NLRP3, and IL-1βwas observed by immunohistochemistry in vivo. Simultaneously, the mRNA and protein levels of TXNIP, NLRP3, procaspase-1, and IL-1βwere significantly induced by high glucose concentration and lipopolysaccharide in a dose-dependent and time-dependent manner in vitro. This induction by both high glucose and lipopolysaccharide was significantly inhibited by N-acetyl-L-cysteine. Our results firstly reveal that high glucose and lipopolysaccharide activate ROS/TXNIP/ NLRP3/IL-1βinflammasome signaling in glomerular mesangial cells, suggesting a mechanism by which inflammation may contribute to the development of diabetic nephropathy.

scholarly journals RIPK2-Mediated Autophagy and Negatively Regulated ROS-NLRP3 Inflammasome Signaling in GMCs Stimulated with High Glucose

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Chenlin Gao ◽  
Jiao Chen ◽  
Fang Fan ◽  
Yang Long ◽  
Shi Tang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Mesangial Cells ◽  
Vital Role ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Interacting Protein ◽  
High Glucose Group ◽  
Glucose Group

Background. Hyperglycemia plays a vital role in diabetic nephropathy (DN); autophagy and its potential upregulator receptor-interacting protein kinase 2 (RIPK2) are associated with ROS, which play a potential role in regulating NLRP3, and may be involved in inflammation in DN. Aim. In this study, we aimed to explore the mechanisms mediated by RIPK2 in autophagy and the relationship with ROS-NLRP3 of DN, by investigating the levels of RIPK2 and autophagy in glomerular mesangial cells (GMCs) stimulated with high glucose. Material and Methods. GMCs were divided into the following groups: normal group (NC), high glucose group (HG), and RIPK2 siRNA group. RIPK2, LC3, caspase1, and IL-1β levels were measured by western blotting and RT-PCR. Autophagosomes were measured by GFP-RFP-LC3; ROS were detected by DCFH-DA. Results. High glucose upregulated RIPK2 and LC3 in GMCs during short periods (0-12 h) (p<0.01), while RIPK2 and LC3 were significantly downregulated in the long term (12-72 h) (p<0.01); these changes were positively correlated with glucose concentration (p<0.01). In addition, levels of ROS, caspase1, and IL-1β increased in a time- and dose-dependent manner in the high glucose group, even with an increased expression of LC3 (p<0.01). However, LC3 expression decreased in the siRIPK2 group, while levels of ROS, caspase1, and IL-1β increased (p<0.01). Conclusions. Autophagy was activated by high glucose at short time periods but was inhibited in the long term, demonstrating a dual role for high glucose in autophagy of GMCs. RIPK2 regulates ROS-NLRP3 inflammasome signaling through autophagy and may be involved in the pathogenesis of DN.

Platelet-activating factor and the kidney

1986 ◽  
Vol 251 (1) ◽  
pp. F1-F11 ◽  
Author(s):  
D. Schlondorff ◽  
R. Neuwirth
Keyword(s):  
De Novo ◽  
Mesangial Cells ◽  
Biological Activities ◽  
Platelet Activating Factor ◽  
Calcium Ionophore ◽  
Initial Step ◽  
Renal Physiology ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Isolated Kidney

Platelet-activating factor (PAF) represents a group of phospholipids with the basic structure of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine. A number of different cells are capable of producing PAF in response to various stimuli. The initial step of PAF formation is activation of phospholipase A2 in a calcium-dependent manner, yielding lyso-PAF. During this step arachidonic acid is also released and can be converted to its respective cyclooxygenase and lipoxygenase products. The lyso-PAF generated is then acetylated in position 2 of the glycerol backbone by a coenzyme A (CoA)-dependent acetyltransferase. An additional pathway may exist whereby PAF is generated de novo from 1-alkyl-2-acetyl-sn-glycerol by phosphocholine transferase. PAF inactivation in cells and blood is by specific acetylhydrolases. PAF exhibits a variety of biological activities including platelet and leukocyte aggregation and activation, increased vascular permeability, respiratory distress, decreased cardiac output, and hypotension. In the kidney PAF can produce decreases in blood flow, glomerular filtration, and fluid and electrolyte excretion. Intrarenal artery injection of PAF may also result in glomerular accumulation of platelets and leukocytes and mild proteinuria. PAF increases prostaglandin formation in the isolated kidney and in cultured glomerular mesangial cells. PAF also causes contraction of mesangial cells. Upon stimulation with calcium ionophore the isolated kidney, isolated glomeruli and medullary cells, and cultured mesangial cells are capable of producing PAF. The potential role for PAF in renal physiology and pathophysiology requires further investigation that may be complicated by 1) the multiple interactions of PAF, prostaglandins, and leukotrienes and 2) the autocoid nature of PAF, which may restrict its action to its site of generation.

scholarly journals Tumour metastasis suppressor, nm23-β, inhibits gelatinase A transcription by interference with transactivator Y-box protein-1 (YB-1)

2002 ◽  
Vol 366 (3) ◽  
pp. 807-816 ◽  
Author(s):  
Sunfa CHENG ◽  
Maria Alexandra ALFONSO-JAUME ◽  
Peter R. MERTENS ◽  
David H. LOVETT
Keyword(s):  
Mesangial Cells ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Repeat Sequence ◽  
Luciferase Reporter ◽  
Metastasis Suppressor ◽  
Gelatinase A ◽  
Glomerular Mesangial Cells ◽  
Tumour Metastasis ◽  
Β Protein

Gelatinase A transcriptional regulation is the consequence of combinatorial interactions with key promoter and enhancer elements identified within this gene. A potent 40bp enhancer response element, RE-1, located in the near 5′ flanking regions of the rat and human gelatinase A genes drives high-level expression in glomerular mesangial cells (MCs). Southwestern-blot analysis of MC nuclear extracts revealed specific interactions of RE-1 with at least four proteins, of which three have been identified as p53, activator protein 2 and the single-stranded DNA-binding factor Y-box protein-1 (YB-1). In the present study, we report the identification of a fourth 17kDa RE-1-binding protein as the rat homologue (nm23-β) of the human nm23-H1 metastasis suppressor gene. Recombinant nm23-β protein bound only the single-stranded forms of the RE-1 sequence. Mutagenesis revealed direct interaction of nm23-β with a repeat sequence, 5′-GGGTTT-3′, shown previously to specifically interact with YB-1 [Mertens, Harendza, Pollock and Lovett (1997) J. Biol. Chem. 272, 22905—22912], and recombinant nm23-β protein competed for single-stranded YB-1 binding. Transient transfection of MC with an nm23-β expression plasmid within the context of a RE-1/simian virus 40 promoter/luciferase reporter yielded a concentration-dependent repression (80—90%) of luciferase activity in MC and Rat1 fibroblasts. A similar pattern of nm23-β repression was demonstrated within the context of the RE-1/homologous gelatinase A promoter. Co-transfection of nm23-β blocked YB-1-mediated activation of transcription and expression of gelatinase A. Nm23-β may be an important physiological regulator of gelatinase A transcription that acts by competitive interference with the single-stranded transactivator YB-1. Gelatinase A is a key mediator of tumour metastasis, suggesting that competitive suppression of transcription by nm23-β (or the human nm23-H1) may be a component of the reduced metastatic capabilities of cells expressing high levels of this protein.

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