Bioinformatics Analysis Identifies Potential Ferroptosis Key Gene in Type 2 Diabetic Islet Dysfunction

Ye, Haowen; Wang, Ruxin; Wei, Jinjing; Wang, Ying; Zhang, Xiaofang; Wang, Lihong

doi:10.3389/fendo.2022.904312

Cited by 10 publications

(3 citation statements)

References 33 publications

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“…Glycolysis in a hyperglycaemic state is closely related to the function of macrophages [46]. MGST1, which is positively correlated with FBG, has been validated as a key T2DM gene involved in problems with islet cells [47][48]. MGST1 is a membrane-bound transferase that regulates oxidative stress [49] and is closely related to chronic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing of peripheral blood mononuclear cells reveals complex cellular signalling signatures of metformin treatment type 2 diabetes mellitus

Zhao,

Fang

2024

Preprint

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ObjectiveType 2 diabetes mellitus (T2DM) is a complex polygenic disease. The onset of the disease is related to autoimmunity. However, how immune cells function in the peripheral blood remains to be elucidated. Metformin is the first-line treatment. Exploring biomarkers of T2DM based on single-cell sequencing technology can provide new insights for the discovery of metformin treatment T2DM in molecular mechanisms.MethodsWe profiled 43,971 cells and 20,228 genes from peripheral blood mononuclear cells (PBMCs) of T2DM patients and healthy controls by single-nucleotide RNA sequencing.ResultsB cells, T cells, monocytes/macrophages, platelets, neutrophils, NK cells and cDC2s were grouped into 7 subclusters. Furthermore, T cells and monocytes/macrophages might be significantly correlated with the clinical characteristics of T2DM patients. RPL27 and AC018755.4 expression were strongly negative correlated with HbA1c. CD4+ T cells are mainly in the memory activation stage, and CD8+ T cells are effectors. The 50 genes whose expression varied with developmental time were associated with cytoplasmic translation, cell‒cell adhesion mediated by integrin, and the regulation of the inflammatory response. Monocytes/macrophages include classic monocytes and nonclassical monocytes. The GSEA results showed that the marker genes were enriched in the HALLMARK_INTERFERON_GAMMA_RESPONSE and HALLMARK_TNFA_SIGNALING_VIA_NFKB. The WGCNA results showed 14 modules. Meanwhile, TNFRSF1A is the most core genes in network interaction. Further analysis revealed ligand‒receptor pairs, including MIF-(CD74 + CD44), MIF-(CD74 + CXCR4), ANXA1-FPR1 and LGALS9-CD45.ConclusionsOur study revealed that the transcriptional map of immune cells from PBMCs provided a framework for understanding the immune status of T2DM patients with metformin treatment via scRNA-seq analysis.

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Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing of peripheral blood mononuclear cells reveals complex cellular signalling signatures of metformin treatment type 2 diabetes mellitus

Zhao,

Fang

2024

Preprint

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“…Evidence shows that Abnormal ferroptosis is closely related to the occurrence and progression of various diseases, including metabolic diseases, such as T2DM. Over the past decade, an increasing number of studies have supported the view that ferroptosis plays an important pathophysiological role in the occurrence and development of T2DM and its complications [19][20][21][22].…”

Section: Molecular Mechanism and Metabolic Basis Of Ferroptosismentioning

confidence: 99%

Iron metabolism and ferroptosis in type 2 diabetes mellitus and complications: mechanisms and therapeutic opportunities

et al. 2023

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The maintenance of iron homeostasis is essential for proper endocrine function. A growing body of evidence suggests that iron imbalance is a key factor in the development of several endocrine diseases. Nowadays, ferroptosis, an iron-dependent form of regulated cell death, has become increasingly recognized as an important process to mediate the pathogenesis and progression of type 2 diabetes mellitus (T2DM). It has been shown that ferroptosis in pancreas β cells leads to decreased insulin secretion; and ferroptosis in the liver, fat, and muscle induces insulin resistance. Understanding the mechanisms concerning the regulation of iron metabolism and ferroptosis in T2DM may lead to improved disease management. In this review, we summarized the connection between the metabolic pathways and molecular mechanisms of iron metabolism and ferroptosis in T2DM. Additionally, we discuss the potential targets and pathways concerning ferroptosis in treating T2DM and analysis the current limitations and future directions concerning these novel T2DM treatment targets.

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“…By analyzing the results, important core modules and molecules can be identified. The introduction of co-expression networks has facilitated a network-based gene selection method, which can be used in basic medical research to identify specific candidate biomarkers [ 14 ] or immunotherapy targets [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Potential mechanisms and drug prediction of Rheumatoid Arthritis and primary Sjögren’s Syndrome: A public databases-based study

Wu,

Wang,

Gao

et al. 2024

PLoS ONE

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Rheumatoid arthritis (RA) and primary Sjögren’s syndrome (pSS) are the most common systemic autoimmune diseases, and they are increasingly being recognized as occurring in the same patient population. These two diseases share several clinical features and laboratory parameters, but the exact mechanism of their co-pathogenesis remains unclear. The intention of this study was to investigate the common molecular mechanisms involved in RA and pSS using integrated bioinformatic analysis. RNA-seq data for RA and pSS were picked up from the Gene Expression Omnibus (GEO) database. Co-expression genes linked with RA and pSS were recognized using weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. Then, we screened two public disease–gene interaction databases (GeneCards and Comparative Toxicogenomics Database) for common targets associated with RA and pSS. The DGIdb database was used to predict therapeutic drugs for RA and pSS. The Human microRNA Disease Database (HMDD) was used to screen out the common microRNAs associated with RA and pSS. Finally, a common miRNA–gene network was created using Cytoscape. Four hub genes (CXCL10, GZMA, ITGA4, and PSMB9) were obtained from the intersection of common genes from WGCNA, differential gene analysis and public databases. Twenty-four drugs corresponding to hub gene targets were predicted in the DGIdb database. Among the 24 drugs, five drugs had already been reported for the treatment of RA and pSS. Other drugs, such as bortezomib, carfilzomib, oprozomib, cyclosporine and zidovudine, may be ideal drugs for the future treatment of RA patients with pSS. According to the miRNA–gene network, hsa-mir-21 may play a significant role in the mechanisms shared by RA and pSS. In conclusion, we identified commom targets as potential biomarkers in RA and pSS from publicly available databases and predicted potential drugs based on the targets. A new understanding of the molecular mechanisms associated with RA and pSS is provided according to the miRNA–gene network.

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Bioinformatics Analysis Identifies Potential Ferroptosis Key Gene in Type 2 Diabetic Islet Dysfunction

Cited by 10 publications

References 33 publications

Single-cell RNA sequencing of peripheral blood mononuclear cells reveals complex cellular signalling signatures of metformin treatment type 2 diabetes mellitus

Single-cell RNA sequencing of peripheral blood mononuclear cells reveals complex cellular signalling signatures of metformin treatment type 2 diabetes mellitus

Iron metabolism and ferroptosis in type 2 diabetes mellitus and complications: mechanisms and therapeutic opportunities

Potential mechanisms and drug prediction of Rheumatoid Arthritis and primary Sjögren’s Syndrome: A public databases-based study

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