Roles of the NLRP3 inflammasome in the pathogenesis of diabetic nephropathy

Qiu, Yueming; Tang, Ling‐Zhi

doi:10.1016/j.phrs.2016.11.004

Cited by 152 publications

(114 citation statements)

References 132 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…Quercetin has been shown to increase microglial activation and potently inhibit pro‐inflammatory factors . In addition, quercetin attenuates NLRP3 inflammatory activation and lipid accumulation in diabetic rats . In our study, we found that the NLRP3 pathway is activated in the brain of db/db mice and that synapses and trophic factors are significantly reduced.…”

Section: Discussionsupporting

confidence: 58%

Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice

Tian

Lü

Shi

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Epidemiological studies have found that diabetes and cognitive dysfunction are closely related. Quercetin has been certified with the effect on improving diabetes mellitus (DM) and cognitive impairment. However, the effect and related mechanism of quercetin on diabetic encephalopathy (DE) are still ambiguous. In this study, we used the db/db mice (diabetic model) to discover whether quercetin could improve DE through the Sirtuin1/NLRP3 (NOD‐, LRR‐ and pyrin domain‐containing 3) pathway. Behavioural results (Morris water maze and new object recognition tests) showed that quercetin (70 mg/kg) improved the learning and memory. Furthermore, quercetin alleviated insulin resistance and the level of fasting blood glucose. Besides, Western blot analysis also showed that quercetin increased the protein expressions of nerve‐ and synapse‐related protein, including postsynapticdensity 93 (PSD93), postsynapticdensity 95 (PSD95), brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of db/db mice. Quercetin also increased the protein expression of SIRT1 and decreased the expression of NLRP3 inflammation‐related proteins, including NLRP3, the adaptor protein ASC and cleaved Caspase‐1, the pro‐inflammatory cytokines IL‐1β and IL‐18. In conclusion, the present results indicate that the SIRT1/NLRP3 pathway may be a crucial mechanism for the neuroprotective effect of quercetin against DE.

show abstract

Section: Discussionsupporting

confidence: 58%

Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice

Tian

Lü

Shi

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…NLRP3 inflammasome activation plays an important role in the pathogenesis of DN (Qiu & Tang, ; Yi et al, ). Researches indicate that inherent renal cells, such as podocytes, mesangial cells, or endothelial cells, can also secrete pro‐inflammatory cytokines (Abais et al, ; Tesch et al, ; Zu et al, ) and may aggravate DN.…”

Section: Discussionmentioning

confidence: 99%

“…Upon detecting cellular stress, NLRP3 recruits and assembles with apoptosis‐associated speck‐like protein containing a caspase recruitment domain and caspase‐1, resulting in the activation of caspase 1 (i.e., an increase in cleaved caspase 1 level) and subsequent maturation of IL‐1β and IL‐18. Recently, a review paper shows that NLRP3 inflammasome activation is also involved in the pathogenesis of DN (Qiu & Tang, ). Cytokines are thought to be released from the activated immune cells.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats

Liu

Hao

Chen

et al. 2018

Phytotherapy Research

View full text Add to dashboard Cite

Rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) has been widely used in China for thousands of years to treat febrile diseases and diabetes. Steroidal saponins from AA show good antidiabetes effects and ameliorate diabetic complications. This study was designed to investigate the effects of sarsasapogenin (Sar), a major sapogenin from AA, on diabetic nephropathy (DN) in rats, and to explore the possible mechanisms. Diabetic rats were divided into 3 groups treated orally with Sar (0, 20, or 60 mg/kg) and carboxymethylcellulose sodium, whereas normal rats for Sar (0 or 60 mg/kg) and carboxymethylcellulose sodium. We found that chronic treatment with Sar for 9 weeks significantly ameliorated renal dysfunction of diabetic rats, as evidenced by decreases in albuminuria, kidney weight index, serum uric acid, and morphologic changes such as extracellular matrix expansion and accumulation (fibronectin and collagen IV levels, etc.). Meanwhile, Sar treatment resulted in decreases in interleukin-18, NLRP3, and activated caspase 1 levels as well as advanced glycation endproducts (AGEs) and their receptor (RAGE) levels in the renal cortex of diabetic rats. However, Sar has no effects on the above indices in the normal rats. Therefore, Sar can markedly ameliorate diabetic nephropathy in rats via inhibition of NLRP3 inflammasome activation and AGEs-RAGE interaction.

show abstract

“…Several researches have reported links between UA metabolism and other proinflammatory pathways [21, 22]. Among them, the convincing one is that UA, as crystals causing cellular necrosis, can activate the inflammasome NLRP3, which consequently induces caspase-1 and its downstream cytokines including IL-1 β and IL-18 [23, 24]. The latter two cytokines have been proved to be potentially expressed on tubular epithelial cells and may closely relate to UA-induced interstitial damage [25].…”

Section: Discussionmentioning

confidence: 99%

Febuxostat Attenuates Renal Damage besides Exerting Hypouricemic Effect in Streptozotocin-Induced Diabetic Rats

Ran

et al. 2017

International Journal of Nephrology

View full text Add to dashboard Cite

Aim. In this study, we aimed to investigate the effects of febuxostat, a novel inhibitor of xanthine oxidase (XO), on renal damage in streptozotocin- (STZ-) induced diabetic rats. Methods. Diabetes was induced by the intraperitoneal injection of STZ in male Sprague-Dawley rats. Sham-injected rats served as controls. The control and diabetic rats were treated with and without febuxostat for 8 weeks, respectively. Fasting blood and 24-h urine samples were collected every 4 weeks. Rat livers were extracted for detecting gene expression, content, and bioactivity of XO. Results. Diabetic rats showed significantly increased serum uric acid (SUA), serum creatinine (SCr), and urea nitrogen (BUN) levels. Daily urinary albumin (UAE), uric acid (UUA), and creatinine (UCr) excretion were also significantly increased in these rats. In diabetic rats, at week 8, febuxostat decreased SUA by 18.9%, while UAA was increased by 52.0%. However, UCr and urinary urea nitrogen (UUN) levels remained unchanged, while SCr and BUN levels decreased by >30% in these rats. Although hepatic gene expression, content, and activity of XO increased significantly in diabetic rats, febuxostat only slightly decreased its content. Conclusions. Febuxostat significantly attenuated renal damage in STZ-induced diabetic rats in addition to exerting hypouricemic effect.

show abstract

Roles of the NLRP3 inflammasome in the pathogenesis of diabetic nephropathy

Cited by 152 publications

References 132 publications

Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice

Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice

Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats

Febuxostat Attenuates Renal Damage besides Exerting Hypouricemic Effect in Streptozotocin-Induced Diabetic Rats

Contact Info

Product

Resources

About