Ferroptosis: A Double-Edged Sword in Gastrointestinal Disease

Xu, Chengfei; Liu, Ziling; Xiao, Jiangwei

doi:10.3390/ijms222212403

Cited by 36 publications

(31 citation statements)

References 139 publications

(164 reference statements)

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“…Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (AA) and linoleic acid, preserve highly oxidizable methylene groups that bridge two double bonds and are the two major substrates for lipid peroxidation (66,95). Compared to the less reactive monounsaturated and saturated fatty acids, PUFAs are ideal targets for attack by ROS, and accumulated cytosolic and lipid ROS serve as potent triggers to oxidize PUFAs to generate lipid peroxides, thus inducing ferroptosis (10,96). The oxidation of PUFAs can be regulated by either an enzymatic reaction, such as a lipoxygenase-mediated reaction, or a nonenzymatic reaction, such as a Fenton-type reaction, in the plasma membrane (57,97).…”

Section: Ferroptosis and Inflammatory Bowel Diseasesmentioning

confidence: 99%

“…The studies thus provide strong evidence that an irondependent accumulation of ROS contributes to ferroptosis. Following these early studies, subsequent works revealed that ferroptosis occurs in many clinical disorders, such as kidney disease, cardiomyopathy, atherosclerosis, neurodegenerative disorders, ischemia/reperfusion (I/R) injury, cancers and immune-mediated diseases, such as diabetes, multiple sclerosis, and asthma (9,10). In comparison, given that most of the published studies have focused on investigating the roles of ferroptosis in cancer (11), knowledge about the involvement and mechanisms of ferroptosis in autoimmune diseases remains largely unclear.…”

Section: Introductionmentioning

confidence: 99%

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Ferroptosis and Autoimmune Diseases

Lai

Wu²,

Wu³

et al. 2022

Front. Immunol.

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Adequate control of autoimmune diseases with an unclear etiology resulting from autoreactivation of the immune system remains a major challenge. One of the factors that trigger autoimmunity is the abnormal induction of cell death and the inadequate clearance of dead cells that leads to the exposure or release of intracellular contents that activate the immune system. Different from other cell death subtypes, such as apoptosis, necroptosis, autophagy, and pyroptosis, ferroptosis has a unique association with the cellular iron load (but not the loads of other metals) and preserves its distinguishable morphological, biological, and genetic features. This review addresses how ferroptosis is initiated and how it contributes to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases. The mechanisms responsible for ferroptosis-associated events are discussed. We also cover the perspective of targeting ferroptosis as a potential therapeutic for patients with autoimmune diseases. Collectively, this review provides up-to-date knowledge regarding how ferroptosis occurs and its significance in autoimmune diseases.

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Section: Ferroptosis and Inflammatory Bowel Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ferroptosis and Autoimmune Diseases

Lai

Wu²,

Wu³

et al. 2022

Front. Immunol.

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“…Free PUFAs cannot induce ferroptosis. After incorporation into membrane lipids, including phospholipids (PLs), the excessive accumulation of oxidized (PUFA-PLs) can contribute to ferroptosis ( Xu et al, 2021 ). Lysophosphatidylcholine acyltransferase 3 and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) are involved in activating and incorporating PUFAs into PLs ( Brown et al, 2019 ).…”

Section: Mechanisms Underlying Ferroptosismentioning

confidence: 99%

Ferroptosis in lymphoma: Emerging mechanisms and a novel therapeutic approach

Zhou

Qin

et al. 2022

Front. Genet.

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Unlike apoptosis, necroptosis, autophagy, and pyroptosis, ferroptosis represents a new type of cell death, which is characterized by iron-dependent lipid peroxidation. This process relies largely on the metabolite reactive oxygen species (ROS), phospholipids containing polyunsaturated fatty acids (PUFA-PL), transition metal iron, intra-, and intercellular signaling events, and environmental stress that regulate cellular metabolism and ROS levels. Recent studies show that ferroptosis plays an important role in tumorigenesis, tumor development, and the treatment of hematological malignancies, including lymphoma. Despite the constant emergence of new drugs, the differences in morphological features, immunophenotypes, biological patterns, rates of onset, and response to treatment in lymphoma pose major therapeutic challenges. Since lymphoma is associated with ferroptosis and shows sensitivity towards it, targeting the potential regulatory factors may regulate lymphoma progression. This has emerged as a research hotspot. This review summarizes the current knowledge on ferroptosis induction and resistance mechanisms, their roles and mechanistic details of ferroptosis in lymphoma suppression and immunity, and finally the treatment strategies for lymphoma by targeting ferroptosis.

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“…Ferroptosis is a form of cell death that differs from apoptosis and pyroptosis, The usual causes are lipid peroxidation, iron accumulation, and cell membrane breakdown. 8 .Some other research had found that ferroptosis can be participant in the regulation of in ammatory bowel disease 9 . Huang et.al indicated that ferroptosis-related hub gene STAT3(signal transducer and activator of transcription 3) mediated the ferroptosis process and promoted ulcerative colitis occured 10 .…”

Section: Introductionmentioning

confidence: 98%

Identification of differentially expressed genes associated with ferroptosis in Crohn’s disease

Zhang

2022

Preprint

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Objective:Ferroptosis-related genes may have a critical regulatory role in the pathogenetic process of Crohn’ disease(CD).The purpose of this study was to identify genes expressed in CD that are associated with ferroptosis and provide direction in the diagnosis and therapy of Crohn's disease. Methods: The data for CD mRNA expression were first gathered from the Gene Expression Omnibus (GEO) database, and two gene sets were selected as major targets (GSE75214 and GSE102133) and analyzed differentially expressed genes.Next,R software (version 4.1.2) was used to analyze the common genes in CD differential expressed genes and ferroptosis-related genes.GO enrichment analysis,KEGG pathway analysis were used to identify differential related pathways and functions.Protein-protein interaction(PPI) analysis was performed to identify target genes.DSigDB website was used to predict potential target drugs for hub genes.Finally, qRT-PCR method were used to detect the expression of these ferroptosis related genes in clinical samples obtained from healthy control and CD patients. Result: According to two GEO datasets, we finally identified 13 ferroptosis DEGs(10 upregulated genes and 2 downregulated genes) in crohn disease with the threshold of p-value < 0.05 and |log2 FC| > 1 and selected for continued analysis.Go enrichment analysis and KEGG pathways results were shown in the following figures.PPI analysis indicate the mutual effect between these genes and filtered out 5 hub genes.Top 10 potential targeted drugs were selected. Finally, the result of qRT-PCR shown that the expression of three genes IL-6,PTGS2 and DUOX2 were different between CD samples and healthy samples.This result was consistent with the results we obtained in the biological information analysis. Conclusion: Bioinformatics analysis identified a total of 13 iron death-associated genes in CD. Three differential genes IL-6,PTG32 and DUOX2 were detected in tissue experiments.Our findings might provide new biomarkers and promising treatment targets in CD.

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Ferroptosis: A Double-Edged Sword in Gastrointestinal Disease

Cited by 36 publications

References 139 publications

Ferroptosis and Autoimmune Diseases

Ferroptosis and Autoimmune Diseases

Ferroptosis in lymphoma: Emerging mechanisms and a novel therapeutic approach

Identification of differentially expressed genes associated with ferroptosis in Crohn’s disease

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