Activation of the NLRP3 inflammasome by RAC1 mediates a new mechanism in diabetic nephropathy

2022 ◽  
Author(s):  
Changjiang Ying ◽  
Zhongyuan Zhou ◽  
Jiao Dai ◽  
Meng Wang ◽  
Jie Xiang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome

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 SEVELAMER CARBONATE MODULATES THE NLRP3 AND NLRP6 INFLAMMASOME EXPRESSION IN PATIENTS WITH DIABETIC NEPHROPATHY

2021 ◽  
Vol 80 (2) ◽  
pp. 125-132
Author(s):  
Grațiela Grădișteanu Pîrcălăbioru ◽  
Mariana-Carmen Chifiriuc ◽  
Roxana Adriana Stoica
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome ◽  
Treatment Plan ◽  
Innate Immune ◽  
Pentraxin 3 ◽  
Quantitative Real Time Pcr ◽  
Blood Samples ◽  
Sevelamer Carbonate

Interaction of microorganisms with the host innate immune system is a crucial factor that could modify diabetes and its associated complications. Recent reports have elucidated the role of NLRP3 inflammasome in diabetes, but to our knowledge there is no data regarding the role of other inflammasomes in diabetes-induced inflammation. To investigate this, blood samples were collected from type 2 diabetes (T2DM) patients with nephropathy as well as from healthy volunteers. After red blood cell lysis, RNA was isolated from all collected blood samples. The expression of NLRP 6, NLRP3, ASC, PRO-IL1Β, and PRO-IL18 was assessed by quantitative Real Time PCR (qRT-PCR). Patients with diabetic nephropathy showed higher NLRP3 inflammasome expression compared to healthy controls whereas no significant differences were observed in case of NLRP6 inflammasome. In addition, Pentraxin 3 expression was elevated in patients with diabetic nephropathy. A detailed analysis of the patient’s clinical data revealed the fact that subjects receiving sevelamer carbonate in their treatment plan harboured low expression of Pentraxin 3 (PTX3) and NLRP3 associated genes.

Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-κB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis

Diabetologia ◽  
2013 ◽  
Vol 57 (2) ◽  
pp. 424-434 ◽  
Author(s):  
Shun-Min Yang ◽  
Shuk-Man Ka ◽  
Hua-Lin Wu ◽  
Yu-Chuan Yeh ◽  
Cheng-Hsiang Kuo ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome

scholarly journals Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy

2015 ◽  
Vol 87 (1) ◽  
pp. 74-84 ◽  
Author(s):  
Khurrum Shahzad ◽  
Fabian Bock ◽  
Wei Dong ◽  
Hongjie Wang ◽  
Stefan Kopf ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

scholarly journals Knockdown of NLRP3 alleviates high glucose or TGFB1-induced EMT in human renal tubular cells

2018 ◽  
Vol 61 (3) ◽  
pp. 101-113 ◽  
Author(s):  
Shan Song ◽  
Duojun Qiu ◽  
Fengwei Luo ◽  
Jinying Wei ◽  
Ming Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
P38 Mapk ◽  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Inflammasome Activation ◽  
Mesenchymal Transition ◽  
Tubular Cells ◽  
Renal Tubular Cells

Tubular injury is one of the crucial determinants of progressive renal failure in diabetic nephropathy (DN), while epithelial-to-mesenchymal transition (EMT) of tubular cells contributes to the accumulation of matrix protein in the diabetic kidney. Activation of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome leads to the maturation of interleukin (IL)-1B and is involved in the pathogenic mechanisms of diabetes. In this study, we explored the role of NLRP3 inflammasome on high glucose (HG) or transforming growth factor-B1 (TGFB1)-induced EMT in HK-2 cells. We evaluated EMT through the expression of α-smooth muscle actin (α-SMA) and E-cadherin as well as the induction of a myofibroblastic phenotype. Reactive oxygen species (ROS) was observed using the confocal microscopy. HG was shown to induce EMT at 48 h, which was blocked byNLRP3silencing or antioxidant N-acetyl-L-cysteine (NAC). We found thatNLRP3interference could inhibit HG-induced ROS. Knockdown ofNLRP3could prevent HG-induced EMT by inhibiting the phosphorylation of SMAD3, P38 MAPK and ERK1/2. In addition, P38 MAPK and ERK1/2 might be involved in HG-induced NLRP3 inflammasome activation. Besides, TGFB1 induced the activation of NLRP3 inflammasome and the generation of ROS, which were blocked byNLRP3interference or NAC. Tubular cells exposed to TGFB1 also underwent EMT, and this could be inhibited byNLRP3shRNA or NAC. These results indicated that knockdown ofNLRP3antagonized HG-induced EMT by inhibiting ROS production, phosphorylation of SMAD3, P38MAPK and ERK1/2, highlighting NLRP3 as a potential therapy target for diabetic nephropathy.

scholarly journals DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Ming Yang ◽  
Shilu Luo ◽  
Na Jiang ◽  
Xi Wang ◽  
Yachun Han ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome ◽  
Protective Role ◽  
Tubular Damage ◽  
Inflammasome Activation ◽  
Compound C ◽  
Nlrp3 Inflammasome Activation ◽  
Amp Activated Protein Kinase ◽  
Relationship Of ◽  
The Relationship

NLRP3-mediated inflammation is closely related to the pathological progression of diabetic nephropathy (DN). DsbA-L, an antioxidant enzyme, plays a protective role in a variety of diseases by inhibiting ER stress and regulating metabolism. However, the relationship of DsbA-L with inflammation, especially the NLRP3 inflammasome, has not been examined. In this study, we note that activation of the NLRP3 inflammasome and exacerbated fibrosis were observed in the kidneys of diabetic DsbA-L-knockout mice and were accompanied by decreased phosphorylation of AMP-activated protein kinase (AMPK). Moreover, correlation analysis shows that the phosphorylation of AMPK was negatively correlated with NLRP3 expression and tubular damage. In addition, the decreased AMPK phosphorylation and NLRP3 activation induced by high glucose (HG) in HK-2 cells could be alleviated by the overexpression of DsbA-L. Interestingly, the protective effect of DsbA-L was eliminated after treatment with compound C, a well-known AMPK inhibitor. Our findings suggest that DsbA-L inhibits NLRP3 inflammasome activation by promoting the phosphorylation of AMPK.

NLRP3 inflammasome negatively regulates podocyte autophagy in diabetic nephropathy

2020 ◽  
Vol 521 (3) ◽  
pp. 791-798 ◽  
Author(s):  
Yun Hou ◽  
Sixiang Lin ◽  
Jun Qiu ◽  
Wangnan Sun ◽  
Menghua Dong ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome

scholarly journals Correction to: novel biphenyl diester derivative AB-38b inhibits NLRP3 inflammasome through Nrf2 activation in diabetic nephropathy

2020 ◽  
Vol 36 (4) ◽  
pp. 389-390 ◽  
Author(s):  
Lei Du ◽  
Jin Wang ◽  
Yibing Chen ◽  
Xizhi Li ◽  
Lei Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome ◽  
Nrf2 Activation
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