Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing?

Soares, José; Fernandes, Fernanda Pereira; Patente, Thiago A.; Monteiro, Maria Beatriz; Parisi, Maria Cândida Ribeiro; Giannella-Neto, Daniel; Corrêa-Giannella, Maria Lúcia; Pontillo, Alessandra

doi:10.1016/j.clim.2017.10.003

Cited by 36 publications

(28 citation statements)

References 19 publications

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“…The NLRP1 inflammasome was initially discovered to respond to the Bacillus anthracis lethal factor. A recent study demonstrated that two NLRP1 gene variants, rs11651270 and rs2670660, are associated with a decreased risk of development of DN, suggesting that NLRP1 may play a critical role in the etiology of DN (Soares et al, 2018). The molecular mechanisms underlying the participation of NLRP1 in CKD, however, remain unclear.…”

Section: Other Inflammasomes and Renal Fibrosismentioning

confidence: 99%

Effect and Regulation of the NLRP3 Inflammasome During Renal Fibrosis

Zhang¹,

Wang²

2020

Front. Cell Dev. Biol.

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Renal fibrosis is a common pathological process where certain primary or secondary kidney diseases can continue to progress to the end-stage of the kidney disease; however, the molecular mechanisms underlying renal fibrosis remain unclear. Recently, research focusing on examining the function of inflammasomes has attracted a great deal of attention, and data derived from these research projects have increased our understanding of the effects and regulation of inflammasomes during renal fibrosis. Based on this, the present review summarizes recent findings in regard to NLRP3 inflammasome functions during various kidney diseases, and these findings indicate that the NLRP3 inflammasome not only mediates the inflammatory response but is also associated with pyroptosis, mitochondrial regulation, and myofibroblast differentiation during renal fibrosis. These novel findings provide us with a more in-depth understanding of the pathogenesis of renal fibrosis and will aid in the identification of new targets that can be used for the prevention and treatment of this disease.

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Section: Other Inflammasomes and Renal Fibrosismentioning

confidence: 99%

Effect and Regulation of the NLRP3 Inflammasome During Renal Fibrosis

Zhang¹,

Wang²

2020

Front. Cell Dev. Biol.

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“…Studies showed that NLRP6 and NLRP7 activated caspase-1 by interacting with the apoptosis-associated speck-like protein (ASC) in vitro, but NLRP1 processes the function-to-find domain (FIND), which enables the inflammasome to interact with pro-caspase-1 without the ASC domain [ 23 ] ( Figure 1 ). A recent study demonstrated the protective effect of NLRP1 in DKD, but the effects of NLRP6 and NLRP7 are unreported [ 24 ].…”

Section: Biology Of Pyroptosismentioning

confidence: 99%

New Insights into the Mechanisms of Pyroptosis and Implications for Diabetic Kidney Disease

Lin

Cheng

et al. 2020

IJMS

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Pyroptosis is one special type of lytic programmed cell death, featured in cell swelling, rupture, secretion of cell contents and remarkable proinflammation effect. In the process of pyroptosis, danger signalling and cellular events are detected by inflammasome, activating caspases and cleaving Gasdermin D (GSDMD), along with the secretion of IL-18 and IL-1β. Pyroptosis can be divided into canonical pathway and non-canonical pathway, and NLRP3 inflammasome is the most important initiator. Diabetic kidney disease (DKD) is one of the most serious microvascular complications in diabetes. Current evidence reported the stimulatory role of hyperglycaemia-induced cellular stress in renal cell pyroptosis, and different signalling pathways have been shown to regulate pyroptosis initiation. Additionally, the inflammation and cellular injury caused by pyroptosis are tightly implicated in DKD progression, aggravating renal fibrosis, glomerular sclerosis and tubular injury. Some registered hypoglycaemia agents exert suppressive activity in pyroptosis regulation pathway. Latest studies also reported some potential approaches to target the pyroptosis pathway, which effectively inhibits renal cell pyroptosis and alleviates DKD in in vivo or in vitro models. Therefore, comprehensively compiling the information associated with pyroptosis regulation in DKD is the main aim of this review, and we try to provide new insights for researchers to dig out more potential therapies of DKD.

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“…Currently, there are only a few studies on this topic, investigating the anti-inflammasome activity of minocycline [ 112 ], curcumin [ 113 ], IL-22 [ 114 ], IL6-receptor blockade [ 115 ], and thrombomodulin gene therapy [ 116 ], with suggestive but not entirely conclusive results. To complicate matters, a protective role of the NLRP1 inflammasome in DKD was recently suggested [ 117 ]. It follows that there remains a need for more determined steps in the direction of understanding the clinical relevance of inflammasome signaling in DKD.…”

Section: Diabetic Kidney Diseasementioning

confidence: 99%

The Inflammasome in Chronic Complications of Diabetes and Related Metabolic Disorders

Menini

Iacobini

Vitale

et al. 2020

Cells

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Diabetes mellitus (DM) ranks seventh as a cause of death worldwide. Chronic complications, including cardiovascular, renal, and eye disease, as well as DM-associated non-alcoholic fatty liver disease (NAFLD) account for most of the morbidity and premature mortality in DM. Despite continuous improvements in the management of late complications of DM, significant gaps remain. Therefore, searching for additional strategies to prevent these serious DM-related conditions is of the utmost importance. DM is characterized by a state of low-grade chronic inflammation, which is critical in the progression of complications. Recent clinical trials indicate that targeting the prototypic pro-inflammatory cytokine interleukin-1β (IL-1 β) improves the outcomes of cardiovascular disease, which is the first cause of death in DM patients. Together with IL-18, IL-1β is processed and secreted by the inflammasomes, a class of multiprotein complexes that coordinate inflammatory responses. Several DM-related metabolic factors, including reactive oxygen species, glyco/lipoxidation end products, and cholesterol crystals, have been involved in the pathogenesis of diabetic kidney disease, and diabetic retinopathy, and in the promoting effect of DM on the onset and progression of atherosclerosis and NAFLD. These metabolic factors are also well-established danger signals capable of regulating inflammasome activity. In addition to presenting the current state of knowledge, this review discusses how the mechanistic understanding of inflammasome regulation by metabolic danger signals may hopefully lead to novel therapeutic strategies targeting inflammation for a more effective treatment of diabetic complications.

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Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing?

Cited by 36 publications

References 19 publications

Effect and Regulation of the NLRP3 Inflammasome During Renal Fibrosis

Effect and Regulation of the NLRP3 Inflammasome During Renal Fibrosis

New Insights into the Mechanisms of Pyroptosis and Implications for Diabetic Kidney Disease

The Inflammasome in Chronic Complications of Diabetes and Related Metabolic Disorders

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