The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in diabetic retinopathy

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Апрель 25, 2023

In the working-age population worldwide, diabetic retinopathy (DR), a prevalent complication of diabetes, is main cause vision impairment. Chronic low-grade inflammation plays an essential role in DR development. Recently, concerning pathogenesis DR, Nod-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome retinal cells has been determined as causal factor. eye, NLRP3 activated by several pathways (such ROS and ATP). The activation NPRP3 leads to secretion inflammatory cytokines interleukin-1β (IL-1β) interleukin-18 (IL-18), pyroptosis, rapid form lytic programmed cell death (PCD). Cells that undergo pyroptosis swell rapture, releasing more factors accelerating progression. This review focuses on mechanisms activate leading DR. present research highlighted some inhibitors NLRP3/pyroptosis novel therapeutic measures treatment.

Язык: Английский

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Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases

Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)

Опубликована: Июль 14, 2022

Pyroptosis is a programmed cell death characterized by swift plasma membrane disruption and subsequent release of cellular contents pro-inflammatory mediators (cytokines), including IL-1β IL-18. It differs from other types such as apoptosis, autophagy, necroptosis, ferroptosis, NETosis in terms its morphology mechanism. As recently discovered form death, pyroptosis has been demonstrated to be involved the progression multiple diseases. Recent studies have also suggested that linked various ocular In this review, we systematically summarized discussed recent scientific discoveries involvement common diseases, diabetic retinopathy, age-related macular degeneration, AIDS-related human cytomegalovirus retinitis, glaucoma, dry eye disease, keratitis, uveitis, cataract. We organized new emerging evidence suggesting signaling pathways may potential therapeutic targets hoping provide summary overall intervention strategies relevant multi-dimensional evaluations for well offer valuable ideas further research development perspective pyroptosis.

Язык: Английский

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Diabetic retinopathy: Involved cells, biomarkers, and treatments

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Авг. 9, 2022

Diabetic retinopathy (DR), a leading cause of vision loss and blindness worldwide, is caused by retinal neurovascular unit dysfunction, its cellular pathology involves at least nine kinds cells, including photoreceptors, horizontal bipolar amacrine ganglion glial cells (Müller astrocytes, microglia), endothelial pericytes, pigment epithelial cells. Its mechanism complicated inflammatory factor production, neovascularization, BRB impairment. However, the has not been completely elucidated. Drug treatment for DR gradually advancing recently. Research on potential drug targets relies upon clear information pathogenesis effective biomarkers. Therefore, we reviewed recent literature diagnostic prognostic biomarkers in terms blood, protein, clinical preclinical therapy (including synthesized molecules natural molecules). This review may provide theoretical basis further research.

Язык: Английский

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Targeting Pyroptosis: A Novel Strategy of Ginseng for the Treatment of Diabetes and Its Chronic Complications

Phytomedicine, Год журнала: 2025, Номер unknown, С. 156430 - 156430

Опубликована: Янв. 1, 2025

Язык: Английский

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Molecular investigation of candidate genes for pyroptosis-induced inflammation in diabetic retinopathy

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Июль 25, 2022

Background Diabetic retinopathy is a diabetic microvascular complication. Pyroptosis, as way of inflammatory death, plays an important role in the occurrence and development retinopathy, but its underlying mechanism has not been fully elucidated. The purpose this study to identify potential pyroptosis-related genes by bioinformatics analysis validation model predict microRNAs (miRNAs) long non-coding RNAs (lncRNAs) interacting with them. Subsequently, competing endogenous RNA (ceRNA) regulatory network structured explore their molecular mechanism. Methods We obtained mRNA expression profile dataset GSE60436 from Gene Expression Omnibus (GEO) database collected 51 PubMmed database. differentially expressed were R software, then eight key interest identified correlation analysis, Ontology (GO) enrichment Kyoto Encyclopedia Genes Genomes (KEGG) pathway protein–protein interaction (PPI) analysis. Then, levels these validated quantitative real-time polymerase chain reaction (qRT-PCR) human retinal endothelial cells high glucose incubation, which was used vitro retinopathy. Western blot performed measure protein gasdermin D (GSDMD), dasdermin E (GSDME) cleaved caspase-3 cells. Moreover, aforementioned further confirmed set. Finally, ceRNA structured, miRNAs lncRNAs interacted CASP3, TLR4, GBP2 predicted. Results A total 13 screened six proliferative patients three samples retinas, including one downregulated gene 12 upregulated genes. showed that there among KEGG GO analyses functional roles results mainly related inflammasome complex, interleukin-1 beta production, NOD-like receptor signaling pathway. In addition, hub genes—CASP3, NLRP3, GBP2, CASP1, CASP4, PYCARD, GBP1—were PPI using Cytoscape software. High increased level GSDMD GSDME, critical effectors pyroptosis, vascular Verified qRT-PCR, all consistent chip. Among them, GBP1, GSE179568 dataset. 20 predicted target 22 potentially bind miRNAs. we constructed expected mediate cellular pyroptosis Conclusion Through data GEO software verification qRT-PCR set, successfully involved associated structured. These findings might improve understanding mechanisms

Язык: Английский

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Natural plant medications for the treatment of retinal diseases: The blood-retinal barrier as a clue

Phytomedicine, Год журнала: 2024, Номер 130, С. 155568 - 155568

Опубликована: Март 24, 2024

Язык: Английский

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Diabetic Neuropathy of the Retina and Inflammation: Perspectives

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(11), С. 9166 - 9166

Опубликована: Май 23, 2023

A clear connection exists between diabetes and atherosclerotic cardiovascular disease. Consequently, therapeutic approaches that target both diseases are needed. Clinical trials currently underway to explore the roles of obesity, adipose tissue, gut microbiota, pancreatic beta cell function in diabetes. Inflammation plays a key role pathophysiology associated metabolic disorders; thus, interest has increased targeting inflammation prevent control Diabetic retinopathy is known as neurodegenerative vascular disease occurs after some years poorly controlled However, increasing evidence points figure diabetes-associated retinal complications. Interconnected molecular pathways, such oxidative stress, formation advanced glycation end-products, contribute inflammatory response. This review describes possible mechanisms changes involve pathways.

Язык: Английский

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Puerarin mitigated LPS‐ATP or HG‐primed endothelial cells damage and diabetes‐associated cardiovascular disease via ROS‐NLRP3 signalling

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(10)

Опубликована: Май 1, 2024

The occurrence and development of diabetic vascular diseases are closely linked to inflammation-induced endothelial dysfunction. Puerarin (Pue), the primary component Pueraria lobata, possesses potent anti-inflammatory properties. However, its vasoprotective role remains elusive. Therefore, we investigated whether Pue can effectively protect against damage induced by diabetes. In study, ameliorated lipopolysaccharide-adenosine triphosphate (LPS-ATP) or HG-primed cytotoxicity apoptosis, while inhibited reactive oxygen species (ROS)-mediated NLR family pyrin domain containing 3 (NLRP3) inflammasome in HUVECs, as evidenced significantly decreased ROS level, NOX4, Caspase-1 activity expression NLRP3, GSDMD, cleaved caspase-1, IL-1β IL-18. Meanwhile, inducer CoCI

Язык: Английский

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Neurovascular Impairment and Therapeutic Strategies in Diabetic Retinopathy

International Journal of Environmental Research and Public Health, Год журнала: 2021, Номер 19(1), С. 439 - 439

Опубликована: Дек. 31, 2021

Diabetic retinopathy has recently been defined as a highly specific neurovascular complication of diabetes. The chronic progression the impairment interdependence units (NVUs) is associated with pathogenesis diabetic retinopathy. NVUs consist neurons, glial cells, and vascular interdependent relationships between these cells are disturbed under conditions. Clinicians should understand update current knowledge impairments in Above all, neuronal cell death an irreversible change, it directly related to vision loss patients Thus, neuroprotective vasoprotective therapies for must be established. Understanding physiological pathological helpful establishing This review focuses on introduces possible protective

Язык: Английский

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Potential therapeutic role of pyroptosis mediated by the NLRP3 inflammasome in type 2 diabetes and its complications

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Окт. 27, 2022

As a new way of programmed cell death, pyroptosis plays vital role in many diseases. In recent years, the relationship between and type 2 diabetes (T2D) has received increasing attention. Although current treatment options for T2D are abundant, occurrence development appear to continue, poor prognosis high mortality patients with remain considerable burden global health system. Numerous studies have shown that mediated by NLRP3 inflammasome can affect progression its complications; targeting potential therapeutic effects. this review, we described molecular mechanism more comprehensively, discussed most updated progress complications, listed some drugs agents anti-pyroptosis Based on available evidence, exploring mechanisms pathway may bring benefits preventing treating drug development.

Язык: Английский

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