Role of Pyroptosis in Diabetes and Its Therapeutic Implications

Mamun, Abdullah Al; Wu, Yanqing; Nasrin, Fatema; Akter, Afroza; Taniya, Masuma Afrin; Munir, Fahad; Jia, Chang; Xiao, Jian

doi:10.2147/jir.s291453

Cited by 41 publications

(24 citation statements)

References 193 publications

(294 reference statements)

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“…In recent years, traditional Chinese medicine has been recommended as adjuvant therapy for DFU patients (120). Herbal products containing phenolic compounds, terpenoids, or glycosides have positively affected managing diabetic complications (121). Activation of NLRP3 inflammasome in diabetic wounds can maintain inflammation and delay the wound healing process, so inhibiting the activation of NLRP3 inflammasome and the production of IL-1b can effectively promote the healing of diabetic wounds.…”

Section: Pyroptosis Inhibitors For the Treatment And Management Of Di...mentioning

confidence: 99%

Pyroptosis and inflammasomes in diabetic wound healing

et al. 2022

Front. Endocrinol.

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Diabetic wound is one of the complications of diabetes and is not easy to heal. It often evolves into chronic ulcers, and severe patients will face amputation. Compared with normal wounds, diabetic wounds have an increased proportion of pro-inflammatory cytokines that are detrimental to the normal healing response. The burden of this disease on patients and healthcare providers is overwhelming, and practical solutions for managing and treating diabetic wounds are urgently needed. Pyroptosis, an inflammatory type of programmed cell death, is usually triggered by the inflammasome. The pyroptosis-driven cell death process is primarily mediated by the traditional signaling pathway caused by caspase -1 and the non-classical signaling pathways induced by caspase -4/5/11. Growing evidence that pyroptosis promotes diabetic complications, including diabetic wounds. In addition, inflammation is thought to be detrimental to wound healing. It is worth noting that the activation of the NLRP3 inflammasome plays a crucial role in the recovery of diabetic wounds. This review has described the mechanisms of pyroptosis-related signaling pathways and their impact on diabetic wounds. It has discussed new theories and approaches to promote diabetic wound healing, as well as some potential compounds targeting pyroptosis and inflammasome signaling pathways that could be new approaches to treating diabetic wounds.

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Section: Pyroptosis Inhibitors For the Treatment And Management Of Di...mentioning

confidence: 99%

Pyroptosis and inflammasomes in diabetic wound healing

et al. 2022

Front. Endocrinol.

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“…We then recognized two distinct pyroptosis clusters for HNSCC patients by consensus clustering analysis based on the 22 PRGs. Because of the highly proinflammatory features and the critical role of pyroptosis in antitumor immunity, 16 , 38 we performed GSVA analysis (which is usually used for predicting the variation in the pathway and biological functions activity in samples 27 ). We found that pyroptosis cluster A was markedly enriched in immune full‐activation pathways such as the chemokine signaling pathway, cytokine‐cytokine receptor interactions, the toll‐like receptor signaling pathway, NK cell‐mediated cytotoxicity, and the NOD‐like receptor signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Pyroptosis patterns and immune infiltrates characterization in head and neck squamous cell carcinoma

Deng

Wei

Qiu

et al. 2022

Clinical Laboratory Analysis

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Background: Pyroptosis plays an essential role in tumor immune responses and inflammation related to chemotherapy. Herein, we studied the characteristic patterns of pyroptosis in head and neck squamous cell carcinoma (HNSCC) to determine their prognostic and therapeutic effects. Methods: Consensus clustering analysis was performed to classify patients into pyroptosis or gene clusters. A novel pyroptosis score was constructed by principal component analysis. Kaplan-Meier survival curves were used to show the prognostic value. We also assessed the functional enrichment, tumor mutation burden, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between high and low pyroptosis score group. Results: Two distinct pyroptosis clusters were defined based on the mRNA expression profiles of PRGs, which were related to immune activation in HNSCC. Notably, a pyroptosis score was constructed according to different expression gene signatures, and then, each HNSCC patient was classified into a low or high pyroptosis score group. Patients with low pyroptosis scores had better immunotherapeutic responses and higher sensitivities to chemotherapeutic agents (paclitaxel, docetaxel, and gemcitabine). Kaplan-Meier survival curves showed that the pyroptosis patterns were independent prognostic indicators regardless of the level of tumor mutation burden. Conclusions: Pyroptosis plays an essential role in immune infiltration in HNSCC. Quantifying the pyroptosis score of individual patients might suggest prognostic, immunotherapeutic, and chemotherapeutic strategies for HNSCC.

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“…The GSDMD-NT is the effector molecule of pyroptosis, which forms membrane pores and then induces the secretion of proinflammatory cytokines ( 36 , 37 ). Accumulating evidence highlights a central role for pyroptosis in the pathogenesis of DM ( 7 , 38 ). An et al reported that blocking pyroptosis and NLRP3 inflammasome activation was effective in mitigating DM-related complications ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

“…And activated caspase-1 cleaves gasdermin D (GSDMD) to generate an N-terminal GSDMD fragment (GSDMD-NT). The GSDMD-NT targets the plasma membrane and results in the formation of a cell pore, cell tumid, and lysis, which initiates a programmed death process referred to as pyroptosis ( 6 , 7 ). In patients with DM, NLRP3 inflammasome is activated, and successive proinflammatory mediators also significantly elevate ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

MiR-17-5p Inhibits TXNIP/NLRP3 Inflammasome Pathway and Suppresses Pancreatic β-Cell Pyroptosis in Diabetic Mice

Liu

Tang

Fu-jian

et al. 2021

Front. Cardiovasc. Med.

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Objective: Diabetes mellitus is a chronic progressive inflammatory metabolic disease with pancreatic β-cells dysfunction. The present study aimed to investigate whether miR-17-5p plays a protective effect on pancreatic β-cells function in diabetes mellitus (DM) mice and dissect the underlying mechanism.Methods: C57BL/6J mice were randomly divided into control, DM, DM + Lentivirus negative control (LV-NC), and DM + Lenti-OE™ miR-17-5p (LV-miR-17-5) groups. DM was established by feeding a high-fat diet and intraperitoneal injection with streptozotocin (STZ) in mice. Blood glucose and glucose tolerance in circulation were measured. Meanwhile, the activation of nod-like receptor protein 3 (NLRP3) inflammasome, pancreas pyroptosis, and the expression of miR-17-5p and thioredoxin-interacting protein (TXNIP) were detected in the pancreas of DM mice. Pancreatic β-cell line INS-1 subjected to different concentrations of glucose was used in in vitro experiments.Results: Compared with control mice, glucose tolerance deficit, elevated blood glucose level, and decreased pancreatic islet size, were presented in DM mice, which was associated with a downregulation of miR-17-5p. Importantly, exogenous miR-17-5p alleviated pancreas injury, and consequently improved glucose tolerance and decreased blood glucose in DM mice. In vitro experiments showed that high glucose decreased miR-17-5p expression and impaired insulin secretion in INS-1 cells. Mechanistically, miR-17-5p inhibited the expression of TXNIP and NLRP3 inflammasome activation, and thus decreased pancreatic β-cell pyroptosis.Conclusion: Our results demonstrated that miR-17-5p improves glucose tolerance, and pancreatic β-cell function and inhibits TXNIP/NLRP3 inflammasome pathway-related pyroptosis in DM mice.

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Role of Pyroptosis in Diabetes and Its Therapeutic Implications

Cited by 41 publications

References 193 publications

Pyroptosis and inflammasomes in diabetic wound healing

Pyroptosis and inflammasomes in diabetic wound healing

Pyroptosis patterns and immune infiltrates characterization in head and neck squamous cell carcinoma

MiR-17-5p Inhibits TXNIP/NLRP3 Inflammasome Pathway and Suppresses Pancreatic β-Cell Pyroptosis in Diabetic Mice

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