scholarly journals NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Pan Gao ◽  
Fang-Fang He ◽  
Hui Tang ◽  
Chun-Tao Lei ◽  
Shan Chen ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Antioxidant Defense System ◽  
Inflammasome Activation ◽  
Podocyte Injury ◽  
Interacting Protein ◽  
Nalp3 Inflammasome ◽  
Thioredoxin Interacting Protein ◽  
A Subunit ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease, and previously we demonstrated that NALP3 inflammasome was involved in the pathogenesis of DN. Here we investigated the mechanisms of NALP3 inflammasome activation in podocyte injury during DN. We found that, besides the activation of NALP3 inflammasome and upregulated thioredoxin-interacting protein (TXNIP), the glomerular expression ofgp91phox, a subunit of NADPH oxidase, was enhanced in DN mice simultaneously. Inhibiting NADPH oxidase abrogated NALP3 inflammasome activation, and IL-1βproduction and eventually protected podocytes from high glucose- (HG-) induced injury. TXNIP, an inhibitor of thioredoxin, acts as a suppressor for antioxidant defense system. Our observation indicated that in HG-exposed podocytes genetic deletion of TXNIP by shRNA reversedgp91phoxoverexpression and alleviated the injury of podocyte. Collectively, our findings proposed that HG-induced NADPH oxidase activation was driven by TXNIP which subsequently triggered NALP3 inflammasome activation in podocytes and ultimately led to podocyte injury, and blocking TXNIP/NADPH oxidase signaling may be a promising treatment for DN.Erratum to “NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia”

Thioredoxin-interacting protein links oxidative stress to inflammasome activation

2009 ◽  
Vol 11 (2) ◽  
pp. 136-140 ◽  
Author(s):  
Rongbin Zhou ◽  
Aubry Tardivel ◽  
Bernard Thorens ◽  
Inpyo Choi ◽  
Jürg Tschopp
Keyword(s):  
Oxidative Stress ◽  
Inflammasome Activation ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

scholarly journals A Pan-cancer Analysis of Thioredoxin-interacting Protein as an Immunological and Prognostic Biomarker

2022 ◽  
Author(s):  
Xuxue Guo ◽  
Mei Huang ◽  
Haonan Zhang ◽  
Qianhui Chen ◽  
Ying Hu ◽  
...  
Keyword(s):  
Immune Cell ◽  
Prognostic Biomarker ◽  
Redox Homeostasis ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Inflammasome Activation ◽  
Post Translational Modification ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Pan Cancer

Abstract BackgroundThe critical role of thioredoxin-interacting protein (TXNIP) in cellular sulfhydryl redox homeostasis and inflammasome activation is already widely known, however, no pan-cancer analysis is currently available. MethodsWe thus first explored the potential roles of TXNIP across thirty-three tumors mainly based on The Cancer Genome Atlas and Gene Expression Omnibus datasets. ResultsTXNIP is lowly expressed in most cancers, and distinct associations exist between TXNIP expression and the prognosis of tumor patients. TXNIP expression was associated with tumor mutational burden, microsatellite instability, mismatch repair genes, tumor infiltrating immune cell abundance as well as cancer-associated fibroblasts. Moreover, ubiquitin mediated proteolysis, protein post-translational modification and other related pathways were involved in the functional mechanisms of TXNIP. ConclusionsOur first pan-cancer study offers a relatively comprehensive understanding of the carcinostatic roles of TXNIP across different tumors. And this molecule may be considered as a potential immunological and prognostic biomarker.

scholarly journals Effects of BSF on Podocyte Apoptosis via Regulating the ROS-Mediated PI3K/AKT Pathway in DN

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Fang-qiang Cui ◽  
Yue-Fen Wang ◽  
Yan-bin Gao ◽  
Yuan Meng ◽  
Zhen Cai ◽  
...  
Keyword(s):  
In Vitro Studies ◽  
Akt Pathway ◽  
Sirna Transfection ◽  
Podocyte Injury ◽  
Nitrogen Levels ◽  
Stage Renal Disease ◽  
End Stage ◽  
Protein Serum

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The ROS-mediated PI3K/AKT pathway plays a key role in podocyte apoptosis and DN progression. Our previous study demonstrated that Baoshenfang (BSF) can decrease proteinuria and attenuate podocyte injury. However, the effects of BSF on podocyte apoptosis induced by the ROS-mediated PI3K/AKT pathway remain unclear. Herein, in vivo and in vitro studies have been performed. In our in vivo study, BSF significantly decreased 24-h urinary protein, serum creatinine, and blood urea nitrogen levels in DN mice. Meanwhile, BSF significantly inhibited oxidative stress and podocyte apoptosis in our in vivo and in vitro studies. Moreover, BSF significantly decreased the inhibition of the PI3K/AKT pathway induced by HG in DN. More importantly, the effects of BSF on podocyte apoptosis were reversed by PI3K siRNA transfection. In conclusion, BSF can decrease proteinuria and podocyte apoptosis in DN, in part through regulating the ROS-mediated PI3K/AKT pathway.

Targeting the NLRP3 Inflammasome in Diabetic Nephropathy

2021 ◽  
Vol 28 ◽  
Author(s):  
Ming Yang ◽  
Xi Wang ◽  
Yachun Han ◽  
Chenrui Li ◽  
Ling Wei ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
End Stage Renal Disease ◽  
Pathological Process ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Relationship

: Diabetic nephropathy (DN) is one of the most common complications of diabetes and the main cause of end-stage renal disease (ESRD). The inflammatory response plays a key role in the pathological process of DN. As the most deeply studied inflammasome, NLRP3 should not be overlooked in DN. Its abnormal activation accelerates DN progression. In this review, we summarize our understanding of the structural composition and activation factors of the NLRP3 inflammasome. Moreover, the relationship between NLRP3 inflammasome activation, and the potential of the NLRP3 inflammasome as a therapeutic target for DN will also be discussed.

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