Pyroptosis and Its Regulation in Diabetic Cardiomyopathy

Lu, Yafang; Lu, Yaqiong; Meng, Jun; Zuo, Wenqi

doi:10.3389/fphys.2021.791848

Cited by 21 publications

(21 citation statements)

References 128 publications

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“…The gray modules represent genes that had not been classified and, therefore, these were deleted. Because of the important effects of pyroptosis on diabetes ( Lu et al, 2021 ), we retrieved pyroptosis-related genes from the GeneCards database ( Stelzer et al, 2016 ), searching for the keyword criteria “pyroptosis”. Module analysis and mining were performed with the characteristics of pyroptosis-related genes to obtain modules significantly related to pyroptosis for further analysis.…”

Section: Methodsmentioning

confidence: 99%

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Comprehensive analysis of key m5C modification-related genes in type 2 diabetes

Song

Jiang

et al. 2022

Front. Genet.

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Background: 5-methylcytosine (m5C) RNA methylation plays a significant role in several human diseases. However, the functional role of m5C in type 2 diabetes (T2D) remains unclear.Methods: The merged gene expression profiles from two Gene Expression Omnibus (GEO) datasets were used to identify m5C-related genes and T2D-related differentially expressed genes (DEGs). Least-absolute shrinkage and selection operator (LASSO) regression analysis was performed to identify optimal predictors of T2D. After LASSO regression, we constructed a diagnostic model and validated its accuracy. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to confirm the biological functions of DEGs. Gene Set Enrichment Analysis (GSEA) was used to determine the functional enrichment of molecular subtypes. Weighted gene co-expression network analysis (WGCNA) was used to select the module that correlated with the most pyroptosis-related genes. Protein-protein interaction (PPI) network was established using the STRING database, and hub genes were identified using Cytoscape software. The competitive endogenous RNA (ceRNA) interaction network of the hub genes was obtained. The CIBERSORT algorithm was applied to analyze the interactions between hub gene expression and immune infiltration.Results: m5C-related genes were significantly differentially expressed in T2D and correlated with most T2D-related DEGs. LASSO regression showed that ZBTB4 could be a predictive gene for T2D. GO, KEGG, and GSEA indicated that the enriched modules and pathways were closely related to metabolism-related biological processes and cell death. The top five genes were identified as hub genes in the PPI network. In addition, a ceRNA interaction network of hub genes was obtained. Moreover, the expression levels of the hub genes were significantly correlated with the abundance of various immune cells.Conclusion: Our findings may provide insights into the molecular mechanisms underlying T2D based on its pathophysiology and suggest potential biomarkers and therapeutic targets for T2D.

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Section: Methodsmentioning

confidence: 99%

“…As pyroptosis and m5C have important effects on diabetes ( Liu et al, 2021 ; Lu et al, 2021 ), we determined if any genes of the pyroptosis module overlapped with m5C-related genes. A PPI network was constructed based on overlapping genes using the STRING database ( von Mering et al, 2003 ).…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of key m5C modification-related genes in type 2 diabetes

Song

Jiang

et al. 2022

Front. Genet.

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“…Subsequent studies have shown that NLRP3 inflammasome activation can aggravate IR and lead to further damage to islet b cells and promote T2D progression (5,112,(116)(117)(118)(119); some recent studies have also demonstrated that the activation of the NLRP3 inflammasome mediates the pyroptosis of pancreatic b cells (108,120); for example, in the study of Yuan, J et al, the use of the NLRP3 inhibitor MCC950 ameliorated islet cell damage (121). Furthermore, pyroptosis mediated by the NLPR3 inflammasome plays a vital role in the progression of various complications such as diabetic nephropathy (DN) and diabetic cardiomyopathy (DCM) (Figure 3) (122)(123)(124)(125). Recent studies have shown the potential therapeutic role of the NLRP3 inflammasome/pyroptosis signaling pathway in type 2 diabetes and its complications.…”

Section: Nlrp3 Inflammasome-mediated Pyroptosis and Type 2 Diabetesmentioning

confidence: 99%

“…Cardiomyocytes maintain the systolic and diastolic functions of the heart and ensure the blood supply of the whole body ( 123 ). Under high glucose conditions, the NLRP3 inflammasome was activated through multiple pathways to induce pyroptosis in CMs.…”

Section: Macrovascular and Cardiac Complicationsmentioning

confidence: 99%

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

Xiao

Guo

et al. 2022

Front. Endocrinol.

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

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“…As a unique and programmed form of cell death, pyroptosis has been revealed to be associated with inflammatory response in DCM via releasing of pro-inflammatory intracellular contents including interleukin (IL)-1β, IL-18, and other inflammatory substances that are induced subsequent to the activation of the NLRP3 inflammasome which is linked to key cardiovascular risk factors ( 107 , 108 ). Meanwhile, emerging evidence has verified the role of non-coding RNAs in the pathogenesis of pyroptosis in DCM ( 109 ), including micro RNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) ( 110 ). Xu et al proved that suppression of NLRP3 inflammasome activation-mediated pyroptosis by targeted miR-34b-3p/AHR axis from long non-coding RNA GAS5 is valuable for the attenuation of DCM ( 111 ).…”

Section: Advance In Diabetic Cardiomyopathymentioning

confidence: 99%

Perspectives for Forkhead box transcription factors in diabetic cardiomyopathy: Their therapeutic potential and possible effects of salvianolic acids

Han

Huang

Xia

et al. 2022

Front. Cardiovasc. Med.

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Diabetic cardiomyopathy (DCM) is the primary cause of morbidity and mortality in diabetic cardiovascular complications, which initially manifests as cardiac hypertrophy, myocardial fibrosis, dysfunctional remodeling, and diastolic dysfunction, followed by systolic dysfunction, and eventually end with acute heart failure. Molecular mechanisms underlying these pathological changes in diabetic hearts are complicated and multifactorial, including but not limited to insulin resistance, oxidative stress, lipotoxicity, cardiomyocytes apoptosis or autophagy, inflammatory response, and myocardial metabolic dysfunction. With the development of molecular biology technology, accumulating evidence illustrates that members of the class O of Forkhead box (FoxO) transcription factors are vital for maintaining cardiomyocyte metabolism and cell survival, and the functions of the FoxO family proteins can be modulated by a wide variety of post-translational modifications including phosphorylation, acetylation, ubiquitination, arginine methylation, and O-glycosylation. In this review, we highlight and summarize the most recent advances in two members of the FoxO family (predominately FoxO1 and FoxO3a) that are abundantly expressed in cardiac tissue and whose levels of gene and protein expressions change as DCM progresses, with the goal of providing valuable insights into the pathogenesis of diabetic cardiovascular complications and discussing their therapeutic potential and possible effects of salvianolic acids, a natural product.

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Pyroptosis and Its Regulation in Diabetic Cardiomyopathy

Cited by 21 publications

References 128 publications

Comprehensive analysis of key m5C modification-related genes in type 2 diabetes

Comprehensive analysis of key m5C modification-related genes in type 2 diabetes

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

Perspectives for Forkhead box transcription factors in diabetic cardiomyopathy: Their therapeutic potential and possible effects of salvianolic acids

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