A new research hot spot: The role of NLRP3 inflammasome activation, a key step in pyroptosis, in diabetes and diabetic complications

Yu, Zi-Wei; Zhang, Jing; Li, Xin; Wang, Ying; Fu, Yuhong; Gao, Xinyuan

doi:10.1016/j.lfs.2019.117138

Cited by 138 publications

(92 citation statements)

References 103 publications

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“…Active caspase-1 cleaves pro-IL-1β to produce mature IL-1β, which, when released, recruits other inflammatory cells and exerts direct cytotoxic effects. In addition, the NLRP3 inflammasome mediates a special type of programmed cell death named pyroptosis, which is inherently inflammatory and is triggered by pathological stimuli through the activation of caspase-1 (25,26). The process of pyroptosis is mediated by Gasdermin (GSDMD), consisting of an amino-terminal cell death region, a carboxyterminal autoinhibitory region, and a central linker domain (27).…”

Section: Components and Function Of The Nlrp3 Inflammasomementioning

confidence: 99%

The NLRP3 Inflammasome and Its Role in T1DM

Sun

Pang

et al. 2020

Front. Immunol.

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The NLRP3 (nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome is a protein complex expressed in cells. It detects danger signals and induces the production of active caspase-1 and the maturation and release of IL (interleukin)-33, IL-18, IL-1β and other cytokines. T1DM (type 1 diabetes mellitus) is defined as a chronic autoimmune disorder characterized by the autoreactive T cell-mediated elimination of insulin-positive pancreatic beta-cells. Although the exact underlying mechanisms are obscure, researchers have proposed that both environmental and genetic factors are involved in the pathogenesis of T1DM. Furthermore, immune responses, including innate and adaptive immunity, play an important role in this process. Recently, the NLRP3 inflammasome, a critical component of innate immunity, was reported to be associated with T1DM. Here, we review the assembly and function of the NLRP3 inflammasome. In addition, the activation and regulatory mechanisms that enhance or attenuate NLRP3 inflammasome activation are discussed. Finally, we focus on the relationship between the NLRP3 inflammasome and T1DM, as well as its potential value for clinical use.

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Section: Components and Function Of The Nlrp3 Inflammasomementioning

confidence: 99%

The NLRP3 Inflammasome and Its Role in T1DM

Sun

Pang

et al. 2020

Front. Immunol.

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“…14,15 Moreover, inhibiting pyroptosis could alleviate diabetic cardiomyopathy, diabetic nephropathy, and diabetic retinopathy. 16 However, whether pyroptosis is involved in diabetes-induced brain injury has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Melatonin exerts neuroprotective effects by inhibiting neuronal pyroptosis and autophagy in STZ‐induced diabetic mice

Che

Yang

et al. 2020

FASEB j.

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Diabetes mellitus (DM) patients are at a higher risk of developing brain injury characterized by neuronal death. Melatonin, a hormone produced by the pineal gland, exerts neuroprotective effects against brain damage. However, the effect of melatonin on diabetes‐induced brain injury has not been elucidated. This study was to evaluate the role of melatonin against neuronal death in DM and to elucidate the underlying mechanisms. Herein, we found that melatonin administration significantly alleviated the neuronal death in both streptozotocin (STZ)‐induced diabetic mice and high glucose (HG)‐treated neuronal cells. Melatonin inhibited neuronal pyroptosis and excessive autophagy, as evidenced by decreased levels of NLRP3, cleaved caspase‐1, GSDMD‐N, IL‐1β, LC3, Beclin1, and ATG12 both in vivo and in vitro. MicroRNA‐214‐3p (miR‐214‐3p) was decreased in DM mice and HG‐treated cells, and such a downregulation was corrected by melatonin, which was accompanied by repression of caspase‐1 and ATG12. Furthermore, downregulation of miR‐214‐3p abrogated the anti‐pyroptotic and anti‐autophagic actions of melatonin in vitro. Our results indicate that melatonin exhibits a neuroprotective effect by inhibiting neuronal pyroptosis and excessive autophagy through modulating the miR‐214‐3p/caspase‐1 and miR‐214‐3p/ATG12 axes, respectively, and it might be a potential agent for the treatment of brain damage in the setting of DM.

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“…Zheng et al (2020) reported a role for GSDME-mediated pyroptosis in cardiac injury. NLRP3-related pyroptosis is involved in the occurrence and development of diabetes mellitus and its associated complications (Yu et al, 2020). Endoplasmic reticulum-related pyroptosis plays a role in the pathogenesis of steatohepatitis.…”

Section: Introductionmentioning

confidence: 99%

miRNA-141 Induced Pyroptosis in Intervertebral Disk Degeneration by Targeting ROS Generation and Activating TXNIP/NLRP3 Signaling in Nucleus Pulpous Cells

Xing

et al. 2020

Front. Cell Dev. Biol.

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The role and mechanism of pyroptosis in intervertebral disk (IVD) degeneration are unclear. MicroRNAs (miRNAs) regulate the viability and function of nucleus pulposus cells (NPCs) in IVDs and are related to pyroptosis. We performed microarray analyses of normal and degenerated nucleus pulposus (NP) to assess the role of pyroptosis and identify key miRNAs in IVD degeneration. We also evaluated the underlying mechanism of miRNA-mediated pyroptosis in NPCs. In addition, we demonstrated the preventative effects of miRNAs on IVD degeneration in a rat model. The levels of the pyroptosis-related proteins cleaved caspase-1, N-terminal gasdermin D (GSDMD), interleukin (IL)-1β, and IL-18 in the degenerative NP were significantly higher than those in the normal NP. miRNA-141 was significantly upregulated in the degenerated NP. miR-141 mimic suppressed the matrix synthesis function of NPCs. By contrast, reactive oxygen species (ROS) generation, and the expression of TXNIP and NLRP3 were significantly downregulated by an miR-141 inhibitor. Furthermore, the miRNA-141 inhibitor prevented the degeneration of IVDs in vivo. Our findings suggest that miRNA-141 induces pyroptosis and extracellular matrix (ECM) catabolism in NPCs by increasing ROS generation and activating TXNIP/NLRP3 signaling. miRNA-141regulated pyroptosis may be a novel therapeutic target for IVD degeneration.

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A new research hot spot: The role of NLRP3 inflammasome activation, a key step in pyroptosis, in diabetes and diabetic complications

Cited by 138 publications

References 103 publications

The NLRP3 Inflammasome and Its Role in T1DM

The NLRP3 Inflammasome and Its Role in T1DM

Melatonin exerts neuroprotective effects by inhibiting neuronal pyroptosis and autophagy in STZ‐induced diabetic mice

miRNA-141 Induced Pyroptosis in Intervertebral Disk Degeneration by Targeting ROS Generation and Activating TXNIP/NLRP3 Signaling in Nucleus Pulpous Cells

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