Mechanism of ferroptosis in hypertensive nephropathy

Chen, Yongzhi; Wang, Kun; Yang, Jie; Zhang, Aixia; Dong, Xiayun; Zhou, Zhaocheng; Li, Tianshu; Ruixia, Fan

doi:10.21037/tau-22-276

Cited by 11 publications

(13 citation statements)

References 20 publications

(18 reference statements)

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“…KEGG pathway analysis further confirmed that the differential lncRNAs associated with ferroptosis were related to metabolism and the IL‐17 signaling pathway. Ferroptosis may contribute to hypertensive nephropathy through processes such as drug metabolism‐cytochrome P450, branched‐chain amino acid (BCAA) metabolism, retinol metabolism, organic and amino acid metabolism, humoral immunity, and more 35,36 . It has been reported that ferroptosis‐related genes may impact the prognosis of tongue squamous cell carcinoma (TSCC) through the IL‐17 signaling pathway 37 .…”

Section: Discussionmentioning

confidence: 99%

A ferroptosis‐related LncRNAs signature for predicting prognoses and screening potential therapeutic drugs in patients with lung adenocarcinoma: A retrospective study

Dong,

Tao,

et al. 2023

Cancer Reports

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BackgroundLung adenocarcinoma (LUAD) has a high mortality rate. Ferroptosis is linked to tumor initiation and progression.AimsThis study aims to develop prognostic models of ferroptosis‐related lncRNAs, evaluate the correlation between differentially expressed genes and tumor microenvironment, and identify prospective drugs for managing LUAD.Methods and ResultsIn this study, transcriptomic and clinical data were downloaded from the TCGA database, and ferroptosis‐related genes were obtained from the FerrDb database. Through correlation analysis, Cox analysis, and the LASSO algorithm for constructing a prognostic model, we found that ferroptosis‐related lncRNA‐based gene signatures (FLncSig) had a strong prognostic predicting ability in the LUAD patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments reconfirmed that ferroptosis is related to receptor‐ligand activity, enzyme inhibitor activity, and the IL‐17 signaling pathway. Next, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) algorithms, and pRRophetic were used to predict immunotherapy response and chemotherapy sensitivity. The IMvigor210 cohort was also used to validate the prognostic model. In the tumor microenvironment, Type_II_IFN_Response and HLA were found to be a group of low‐risk pathways, while MHC_class_I was a group of high‐risk pathways. Patients in the high‐risk subgroup had lower TIDE scores. Exclusion, MDSC, CAF, and TAMM2 were significantly and positively correlated with risk scores. In addition, we found 15 potential therapeutic drugs for LUAD. Finally, differential analysis of stemness index based on mRNA expression (mRNAsi) indicated that mRNAsi was correlated with gender, primary tumor (T), distant metastasis (M), and the tumor, node, and metastasis (TNM) stage in LUAD patients.ConclusionsIn conclusion, the prognostic model based on FLncSig can alleviate the difficulty in predicting the prognosis and immunotherapy of LUAD patients. The identified FLncSig and the screened drugs exhibit potential for clinical application and provide references for the treatment of LUAD.

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Section: Discussionmentioning

confidence: 99%

A ferroptosis‐related LncRNAs signature for predicting prognoses and screening potential therapeutic drugs in patients with lung adenocarcinoma: A retrospective study

Dong,

Tao,

et al. 2023

Cancer Reports

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“…[43] Ferroptosis associated with ALB may act in hypertension through pathways such as retinol metabolism, branched-chain amino acid metabolism, drug metabolism-cytochrome P450 and biological processes. [44] PE showed elevated gene and protein expression of NOX4, one of the causes of cellular ROS. Vascular pathogenic diseases have been conclusively associated with excessive ROS production.…”

Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis-related genes in syncytiotrophoblast-derived extracellular vesicles of preeclampsia

Xiang

et al. 2022

Medicine

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Preeclampsia (PE), defined as new-onset hypertension and multi-organ systemic complication during pregnancy, is the leading cause of maternal and neonatal mortality and morbidity. With extracellular vesicles research progresses, current data refers to the possibility that ferroptosis may play a role in exosomal effects. Evidence has suggested that ferroptosis may contribute to the pathogenesis of preeclampsia by bioinformatics analyses. The purpose of the current study is to identify the potential ferroptosisrelated genes in syncytiotrophoblast-derived extracellular vesicles (STB-EVs) of preeclampsia using bioinformatics analyses. Clinical characteristics and gene expression data of all samples were obtained from the NCBI GEO database. The differentially expressed mRNAs (DE-mRNAs) in STB-EVs of preeclampsia were screened and then were intersected with ferroptosis genes. Functional and pathway enrichment analyses of ferroptosis-related DE-mRNAs in STB-EVs were performed. Ferroptosis-related hub genes in STB-EVs were identified by Cytoscape plugin CytoHubba with a Degree algorithm using a protein-protein interaction network built constructed from the STRING database. The predictive performance of ferroptosis-related hub genes was determined by a univariate analysis of receiver operating characteristic (ROC). The miRNA-hub gene regulatory network was constructed using the miRwalk database. A total of 1976 DE-mRNAs in STB-EVs were identified and the most enriched item identified by gene set enrichment analysis was signaling by G Protein-Coupled Receptors (normalized enrichment score = 1.238). These DE-mRNAs obtained 26 ferroptosis-related DE-mRNAs. Ferroptosis-related DE-mRNAs of gene ontology terms and Encyclopedia of Genes and Genomes pathway enrichment analysis were enriched significantly in response to oxidative stress and ferroptosis. Five hub genes (ALB, NOX4, CDKN2A, TXNRD1, and CAV1) were found in the constructed protein-protein interaction network with ferroptosis-related DE-mRNAs and the areas under the ROC curves for ALB, NOX4, CDKN2A, TXNRD1, and CAV1 were 0.938 (CI: 0.815−1.000), 0.833 (CI: 0.612−1.000), 0.875 (CI: 0.704−1.000), 0.958 (CI: 0.862−1.000), and 0.854 (CI: 0.652−1.000) in univariate analysis of ROC. We constructed a regulatory network of miRNA-hub gene and the findings demonstrate that hsa-miR-26b-5p, hsa-miR-192-5p, hsa-miR-124-3p, hsa-miR-492, hsa-miR-34a-5p and hsa-miR-155-5p could regulate most hub genes. In this study, we identified several central genes closely related to ferroptosis in STB-EVs (ALB, NOX4, CDKN2A, TXNRD1, and CAV1) that are potential biomarkers related to ferroptosis in preeclampsia. Our findings will provide evidence for the involvement of ferroptosis in preeclampsia and improve the understanding of ferroptosis-related molecular pathways in the pathogenesis of preeclampsia.Abbreviations: ALB = albumin, CAV1 = caveolin 1, CDKN2A = cyclin dependent kinase inhibitor 2A, DEGs = differentially expressed genes, DE-mRNAs = differentially expressed mRNAs, EVs = extracellular v...

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“…All three databases used the keywords “non‐alcoholic fatty liver disease” and “liver cancer.” The related targets downloaded from these three databases were merged and then deduplicated to get the potential targets. Venny 2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html) (Chen et al, 2022) online tool was used to draw Venn diagram to realize the core target between “Coptidis Rhizoma”, “Evodiae Fructus” and “NAFLD‐related liver cancer”.…”

Section: Methodsmentioning

confidence: 99%

“…Venny 2.1 (https://bioin fogp.cnb. csic.es/tools/ venny/ index.html) (Chen et al, 2022) online tool was used to draw Venn diagram to realize the core target between "Coptidis Rhizoma", "Evodiae Fructus" and "NAFLD-related liver cancer".…”

Section: Nafld-associated Liver Cancermentioning

confidence: 99%

Coptidis rhizoma and evodiae fructus against lipid droplet deposition in nonalcoholic fatty liver disease‐related liver cancer by AKT

Hao

Deng

et al. 2023

Chem Biol Drug Des

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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. NAFLD has become one of the major factors contributing to hepatocellular carcinoma (HCC) development. However, there are no clear targets and therapeutic drugs for NAFLD‐related liver cancer. This study explored the active compounds, target and mechanism of coptidis rhizoma and evodiae fructus in the treatment of NAFLD‐related liver cancer based on the network pharmacology and experimental verification. There were 455 intersection targets of NAFLD‐related liver cancer, and 65 drug‐disease common targets. AKT1 has the highest degree, indicating that it may be a key target of coptidis rhizoma and evodiae fructus in the treatment of NAFLD‐related liver cancer. The expression level of AKT1 was high in high‐risk group, and the overall survival rate was lower than that in low‐risk group. After oleic acid induction, p‐AKT expression and lipid droplet deposition were promoted in HepG2 cells. Quercetin and resveratrol reduced lipid droplet deposition in vivo. Moreover, quercetin inhibited p‐AKT expression, resveratrol both reduced the expression of p‐AKT and AKT. The overall findings suggested that quercetin inhibited AKT in the treatment of NAFLD‐related liver cancer.

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Mechanism of ferroptosis in hypertensive nephropathy

Cited by 11 publications

References 20 publications

A ferroptosis‐related LncRNAs signature for predicting prognoses and screening potential therapeutic drugs in patients with lung adenocarcinoma: A retrospective study

A ferroptosis‐related LncRNAs signature for predicting prognoses and screening potential therapeutic drugs in patients with lung adenocarcinoma: A retrospective study

Identification of ferroptosis-related genes in syncytiotrophoblast-derived extracellular vesicles of preeclampsia

Coptidis rhizoma and evodiae fructus against lipid droplet deposition in nonalcoholic fatty liver disease‐related liver cancer by AKT

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