GW0742 activates miR‐17‐5p and inhibits TXNIP/NLRP3‐mediated inflammation after hypoxic‐ischaemic injury in rats and in PC12 cells

Gamdzyk, Marcin; Doycheva, Desislava; Kang, Ruiqing; Tang, Hong; Travis, Zackary D; Tang, Jiping; Zhang, Junyi

doi:10.1111/jcmm.15698

Cited by 32 publications

(30 citation statements)

References 61 publications

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“…Finally, although poorly investigated, NRs also control Nlrp3 mRNA post-transcriptional stability through the regulation of miRNA. Indeed, the PPAR β / δ agonist, GW0742, significantly reduces the number of activated pro-inflammatory microglial cells after hypoxia–ischemia in neonatal rat brain ( 134 ). This effect is mainly due to a decrease in TXNIP, NLRP3, IL-6 and TNFα ( 134 ).…”

Section: Nuclear Receptors In the Priming Of Nlrp3mentioning

confidence: 99%

“…Indeed, the PPAR β / δ agonist, GW0742, significantly reduces the number of activated pro-inflammatory microglial cells after hypoxia–ischemia in neonatal rat brain ( 134 ). This effect is mainly due to a decrease in TXNIP, NLRP3, IL-6 and TNFα ( 134 ). At the molecular level, the PPAR β / δ antagonist GSK3787 and the miR-17-5p inhibitor abolish GW0742 effect, thus demonstrating the dependency of GW0742 on the PPAR β / δ -miR-17-5p axis ( 134 ) ( Figure 1 ).…”

Section: Nuclear Receptors In the Priming Of Nlrp3mentioning

confidence: 99%

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Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway

Duez

Pourcet

2021

Front. Endocrinol.

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The innate immune system is the first line of defense specialized in the clearing of invaders whether foreign elements like microbes or self-elements that accumulate abnormally including cellular debris. Inflammasomes are master regulators of the innate immune system, especially in macrophages, and are key sensors involved in maintaining cellular health in response to cytolytic pathogens or stress signals. Inflammasomes are cytoplasmic complexes typically composed of a sensor molecule such as NOD-Like Receptors (NLRs), an adaptor protein including ASC and an effector protein such as caspase 1. Upon stimulation, inflammasome complex components associate to promote the cleavage of the pro-caspase 1 into active caspase-1 and the subsequent activation of pro-inflammatory cytokines including IL-18 and IL-1β. Deficiency or overactivation of such important sensors leads to critical diseases including Alzheimer diseases, chronic inflammatory diseases, cancers, acute liver diseases, and cardiometabolic diseases. Inflammasomes are tightly controlled by a two-step activation regulatory process consisting in a priming step, which activates the transcription of inflammasome components, and an activation step which leads to the inflammasome complex formation and the subsequent cleavage of pro-IL1 cytokines. Apart from the NF-κB pathway, nuclear receptors have recently been proposed as additional regulators of this pathway. This review will discuss the role of nuclear receptors in the control of the NLRP3 inflammasome and the putative beneficial effect of new modulators of inflammasomes in the treatment of inflammatory diseases including colitis, fulminant hepatitis, cardiac ischemia–reperfusion and brain diseases.

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Section: Nuclear Receptors In the Priming Of Nlrp3mentioning

confidence: 99%

Section: Nuclear Receptors In the Priming Of Nlrp3mentioning

confidence: 99%

Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway

Duez

Pourcet

2021

Front. Endocrinol.

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“…TXNIP is also a regulatory target of miRNAs in pyroptosis. While an axis miR-497/TXNIP has been described in diabetic nephropathy, other studies report the role of different miRNAs, including miR-17 in the TXNIP/NLRP3 signaling pathway in inflammation-induced kidney injury or brain ischemia [ 123 , 124 , 125 , 128 , 132 ].…”

Section: Txnip Is a Multifunctional Proteinmentioning

confidence: 99%

“…TXNIP is also involved in neonatal hypoxic-ischemia, which occurs in the youngest neonates. In rat models of the disease, PPAR-β/δ agonist mitigates apoptosis and reduces NLRP3-related neuroinflammation by increasing the miR-17-5p level and decreasing TXNIP expression [ 124 , 125 ]. The PPAR-β/δ/miR-17/TXNIP pathway is able to control TXNIP expression and subsequently inhibits NLRP3 activation [ 231 ].…”

Section: Txnip Is a Novel Marker In Cardiovascular Diseasesmentioning

confidence: 99%

The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

Domingues

Jolibois

Rougé

et al. 2021

IJMS

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Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel identified target for preventive and curative medicine. The goal of this review is to focus on the novelties concerning TXNIP. After an overview in TXNIP involvement in oxidative stress, inflammation and metabolism, the remainder of this review presents the clues used to define TXNIP as a new marker at the genetic, blood, or ischemic site level in the context of cardiovascular and ischemic diseases.

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“…Promoting TXNIP activation in vivo using a TXNIP CRISPR activation plasmid reversed the protective effects, as did the administration of a PPAR-β/δ antagonist. The consequence of PPAR-β/δ activation by GW0742 was decreased TXNIP, NLRP3, IL-6, and TNF-α and reduced numbers of activated microglia [ 116 ]. Similar results from PPAR activation were observed in vitro using PC12 neuronal-like cells subjected to oxygen/glucose deprivation (OGD) [ 116 ].…”

Section: Txnip Expression In the Brainmentioning

confidence: 99%

Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases

Tsubaki

Tooyama

Walker

2020

IJMS

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The development of new therapeutic approaches to diseases relies on the identification of key molecular targets involved in amplifying disease processes. One such molecule is thioredoxin-interacting protein (TXNIP), also designated thioredoxin-binding protein-2 (TBP-2), a member of the α-arrestin family of proteins and a central regulator of glucose and lipid metabolism, involved in diabetes-associated vascular endothelial dysfunction and inflammation. TXNIP sequesters reduced thioredoxin (TRX), inhibiting its function, resulting in increased oxidative stress. Many different cellular stress factors regulate TXNIP expression, including high glucose, endoplasmic reticulum stress, free radicals, hypoxia, nitric oxide, insulin, and adenosine-containing molecules. TXNIP is also directly involved in inflammatory activation through its interaction with the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome complex. Neurodegenerative diseases such as Alzheimer’s disease have significant pathologies associated with increased oxidative stress, inflammation, and vascular dysfunctions. In addition, as dysfunctions in glucose and cellular metabolism have been associated with such brain diseases, a role for TXNIP in neurodegeneration has actively been investigated. In this review, we will focus on the current state of the understanding of possible normal and pathological functions of TXNIP in the central nervous system from studies of in vitro neural cells and the brains of humans and experimental animals with reference to other studies. As TXNIP can be expressed by neurons, microglia, astrocytes, and endothelial cells, a complex pattern of regulation and function in the brain is suggested. We will examine data suggesting TXNIP as a therapeutic target for neurodegenerative diseases where further research is needed.

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GW0742 activates miR‐17‐5p and inhibits TXNIP/NLRP3‐mediated inflammation after hypoxic‐ischaemic injury in rats and in PC12 cells

Cited by 32 publications

References 61 publications

Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway

Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway

The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases

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