Identification of Key Pyroptosis-Related Genes and Distinct Pyroptosis-Related Clusters in Periodontitis

Ning, Wanchen; Acharya, Aneesha; Li, Simin; Schmalz, Gerhard; Huang, Shaohong

doi:10.3389/fimmu.2022.862049

Cited by 15 publications

(14 citation statements)

References 89 publications

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“…The NLRP3/caspase-1/GSDMD pathway leads to pyroptosis and is significantly related to inflammation. Pyroptosis has been recently suggested as one of the pathways implicated in the pathogenesis of periodontitis [ 8 , 9 ]. In addition, hyperglycemia, the hallmark of diabetes mellitus, impairs the function of macrophage and induces pyroptosis, which contributes to cell senescence and low-degree inflammatory state in periodontal tissue [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis

Zhao

et al. 2023

IJMS

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Macrophage pyroptosis drives the secretion of IL-1β, which has been recently reported to be a featured salivary biomarker for discriminating periodontitis in the presence of diabetes. This study aimed to explore whether macrophage pyroptosis plays a role in the development of diabetes mellitus–periodontitis, as well as potential therapeutic strategies. By establishing a model of experimental diabetes mellitus–periodontitis in rats, we found that IL-1β and gasdermin D were highly expressed, leading to aggravated destruction of periodontal tissue. MCC950, a potent and selective molecule inhibitor of the NLRP3 inflammasome, effectively inhibited macrophage pyroptosis and attenuated alveolar bone losses in diabetes mellitus–periodontitis. Consistently, in vitro, high glucose could induce macrophage pyroptosis and thus promoted IL-1β production in macrophages stimulated by lipopolysaccharide. In addition, autophagy blockade by high glucose via the mTOR-ULK1 pathway led to severe oxidative stress response in macrophages stimulated by lipopolysaccharide. Activation of autophagy by rapamycin, clearance of mitochondrial ROS by mitoTEMPO, and inhibition of inflammasome by MCC950 could significantly reduce macrophage pyroptosis and IL-1β secretion. Our study demonstrates that hyperglycemia promotes IL-1β production and pyroptosis in macrophages suffered by periodontal microbial stimuli. Modulation of autophagy activity and specific targeting of the ROS-inflammasome pathway may offer promising therapeutic strategies to alleviate diabetes mellitus–periodontitis.

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Section: Introductionmentioning

confidence: 99%

Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis

Zhao

et al. 2023

IJMS

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“…We also found correlations between the 17 pyroptosis-related hub genes and 13 immune cell types. The relationship between pyroptosis regulators and immune infiltrate characterization has been discussed in diseases, including cancer and periodontitis (99,100). In this study, we identified 11 cell types from the scRNA-seq dataset.…”

Section: Discussionmentioning

confidence: 99%

Bulk and single-cell transcriptome analyses of islet tissue unravel gene signatures associated with pyroptosis and immune infiltration in type 2 diabetes

Song

Jiang

et al. 2023

Front. Endocrinol.

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IntroductionType 2 diabetes (T2D) is a common chronic heterogeneous metabolic disorder. However, the roles of pyroptosis and infiltrating immune cells in islet dysfunction of patients with T2D have yet to be explored. In this study, we aimed to explore potential crucial genes and pathways associated with pyroptosis and immune infiltration in T2D.MethodsTo achieve this, we performed a conjoint analysis of three bulk RNA-seq datasets of islets to identify T2D-related differentially expressed genes (DEGs). After grouping the islet samples according to their ESTIMATE immune scores, we identified immune- and T2D-related DEGs. A clinical prediction model based on pyroptosis-related genes for T2D was constructed. Weighted gene co-expression network analysis was performed to identify genes positively correlated with pyroptosis-related pathways. A protein–protein interaction network was established to identify pyroptosis-related hub genes. We constructed miRNA and transcriptional networks based on the pyroptosis-related hub genes and performed functional analyses. Single-cell RNA-seq (scRNA-seq) was conducted using the GSE153885 dataset. Dimensionality was reduced using principal component analysis and t-distributed statistical neighbor embedding, and cells were clustered using Seurat. Different cell types were subjected to differential gene expression analysis and gene set enrichment analysis (GSEA). Cell–cell communication and pseudotime trajectory analyses were conducted using the samples from patients with T2D.ResultsWe identified 17 pyroptosis-related hub genes. We determined the abundance of 13 immune cell types in the merged matrix and found that these cell types were correlated with the 17 pyroptosis-related hub genes. Analysis of the scRNA-seq dataset of 1892 islet samples from patients with T2D and controls revealed 11 clusters. INS and IAPP were determined to be pyroptosis-related and candidate hub genes among the 11 clusters. GSEA of the 11 clusters demonstrated that the myc, G2M checkpoint, and E2F pathways were significantly upregulated in clusters with several differentially enriched pathways.DiscussionThis study elucidates the gene signatures associated with pyroptosis and immune infiltration in T2D and provides a critical resource for understanding of islet dysfunction and T2D pathogenesis.

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“…Finally, we used the "normalize between arrays" function of the "limma" package to reduce the effect of batch effects [ 19 ]. We downloaded a total of 2052 genes related to oxidative stress from MsigDB ( http://www.gsea-msigdb.org/gsea/downloads.jsp ) [ 20 ], GeneCards ( https://www.genecards.org/ ) [ 21 ], and NCBI ( https://www.ncbi.nlm.nih.gov/ ) databases [ 22 ]. 1387 genes related to mitochondrial stress were identified from the MsigDB database and Human MitoCarta 3.0 ( https://www.broadinstitute.org/mitocarta/ ) database [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Identification and validation of a novel prognostic signature based on mitochondria and oxidative stress related genes for glioblastoma

Tong

Xia

et al. 2023

J Transl Med

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Background Mitochondria represent a major source of reactive oxygen species (ROS) in cells, and the direct increase in ROS content is the primary cause of oxidative stress, which plays an important role in tumor proliferation, invasion, angiogenesis, and treatment. However, the relationship between mitochondrial oxidative stress-related genes and glioblastoma (GBM) remains unclear. This study aimed to investigate the value of mitochondria and oxidative stress-related genes in the prognosis and therapeutic targets of GBM. Methods We retrieved mitochondria and oxidative stress-related genes from several public databases. The LASSO regression and Cox analyses were utilized to build a risk model and the ROC curve was used to assess its performance. Then, we analyzed the correlation between the model and immunity and mutation. Furthermore, CCK8 and EdU assays were utilized to verify the proliferative capacity of GBM cells and flow cytometry was used to analyze apoptosis rates. Finally, the JC-1 assay and ATP levels were utilized to detect mitochondrial function, and the intracellular ROS levels were determined using MitoSOX and BODIPY 581/591 C11. Results 5 mitochondrial oxidative stress-related genes (CTSL, TXNRD2, NUDT1, STOX1, CYP2E1) were screened by differential expression analysis and Cox analysis and incorporated in a risk model which yielded a strong prediction accuracy (AUC value = 0.967). Furthermore, this model was strongly related to immune cell infiltration and mutation status and could identify potential targeted therapeutic drugs for GBM. Finally, we selected NUDT1 for further validation in vitro. The results showed that NUDT1 was elevated in GBM, and knockdown of NUDT1 inhibited the proliferation and induced apoptosis of GBM cells, while knockdown of NUDT1 damaged mitochondrial homeostasis and induced oxidative stress in GBM cells. Conclusion Our study was the first to propose a prognostic model of mitochondria and oxidative stress-related genes, which provided potential therapeutic strategies for GBM patients.

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Identification of Key Pyroptosis-Related Genes and Distinct Pyroptosis-Related Clusters in Periodontitis

Cited by 15 publications

References 89 publications

Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis

Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis

Bulk and single-cell transcriptome analyses of islet tissue unravel gene signatures associated with pyroptosis and immune infiltration in type 2 diabetes

Identification and validation of a novel prognostic signature based on mitochondria and oxidative stress related genes for glioblastoma

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