Therapeutic Implications of Ferroptosis in Renal Fibrosis

Zhang, Yao; Mou, Yanhua; Zhang, Jianjian; Suo, Chuanjian; Zhou, Hai; Gu, Min; Wang, Zengjun; Tan, Ruoyun

doi:10.3389/fmolb.2022.890766

Cited by 16 publications

(10 citation statements)

References 293 publications

(336 reference statements)

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“…More specifically, increased expression of renal prostaglandin-endoperoxide synthase (Ptgs2) as a putative marker of ferroptosis was observed in the kidneys. Other ferroptosis-related molecules, including GPXs, iron and lipid peroxides have also been demonstrated (Sponsel et al, 1996; Frontiers in Molecular Biosciences frontiersin.org Himmelfarb, 2005;Zhang et al, 2022), corroborating the involvement of ferroptosis in the pathogenesis of renal fibrosis. Transforming growth factor β1 (TGF-β1) was shown to be a key mediator of renal fibrosis (Ikeda et al, 2014).…”

Section: Ferroptosis Regulatory Genes In Chronic Kidney Diseasementioning

confidence: 66%

Mechanisms of ferroptosis in chronic kidney disease

Zhuo

Wen

Luo

et al. 2022

Front. Mol. Biosci.

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Ferroptosis is a newly identified form of regulated cell death characterized by iron accumulation and lipid peroxidation. Ferroptosis plays an essential role in the pathology of numerous diseases and has emerged as a key area of focus in studies of chronic kidney disease (CKD). CKD is a major public health problem with high incidence and mortality that is characterized by a gradual loss of kidney function over time. The severity and complexity of CKD combined with the limited knowledge of its underlying molecular mechanism(s) have led to increased interest in this disease area. Here, we summarize recent advances in our understanding of the regulatory mechanism(s) of ferroptosis and highlight recent studies describing its role in the pathogenesis and progression of CKD. We further discuss the potential therapeutic benefits of targeting ferroptosis for the treatment of CKD and the major hurdles to overcome for the translation of in vitro studies into the clinic.

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Section: Ferroptosis Regulatory Genes In Chronic Kidney Diseasementioning

confidence: 66%

Mechanisms of ferroptosis in chronic kidney disease

Zhuo

Wen

Luo

et al. 2022

Front. Mol. Biosci.

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“…As a significant characteristic of chronic kidney disease (CKD), renal fibrosis can lead to the loss of the damage of kidney structure and function ( 18 ). An increasing health burden is posed by CKD and renal fibrosis, which affect 10% of the world’s population ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic model constructed by five EMT-related genes for renal fibrosis and reflecting the condition of immune-related cells

Guo

Yuan

et al. 2023

Front. Immunol.

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BackgroundRenal fibrosis is a physiological and pathological characteristic of chronic kidney disease (CKD) to end-stage renal disease. Since renal biopsy is the gold standard for evaluating renal fibrosis, there is an urgent need for additional non-invasive diagnostic biomarkers.MethodsWe used R package “limma” to screen out differently expressed genes (DEGs) based on Epithelial-mesenchymal transformation (EMT), and carried out the protein interaction network and GO, KEGG enrichment analysis of DEGs. Secondly, the least absolute shrinkage and selection operator (LASSO), random forest tree (RF), and support vector machine-recursive feature elimination (SVM-RFE) algorithms were used to identify candidate diagnostic genes. ROC curves were plotted to evaluate the clinical diagnostic value of these genes. In addition, mRNA expression levels of candidate diagnostic genes were analyzed in control samples and renal fibrosis samples. CIBERSORT algorithm was used to evaluate immune cells level. Additionally, gene set enrichment analysis (GSEA) and drug sensitivity were conducted.ResultsAfter obtaining a total of 24 DEGs, we discovered that they were mostly involved in several immunological and inflammatory pathways, including NF-KappaB signaling, AGE-RAGE signaling, and TNF signaling. Five genes (COL4A2, CXCL1, TIMP1, VCAM1, and VEGFA) were subsequently identified as biomarkers for renal fibrosis through machine learning, and their expression levels were confirmed by validation cohort data sets and in vitro RT-qPCR experiment. The AUC values of these five genes demonstrated significant clinical diagnostic value in both the training and validation sets. After that, CIBERSORT analysis showed that these biomarkers were strongly associated with immune cell content in renal fibrosis patients. GSEA also identifies the potential roles of these diagnostic genes. Additionally, diagnostic candidate genes were found to be closely related to drug sensitivity. Finally, a nomogram for diagnosing renal fibrosis was developed.ConclusionCOL4A2, CXCL1, TIMP1, VCAM1, and VEGFA are promising diagnostic biomarkers of tissue and serum for renal fibrosis.

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“…Thus, there is an urgent need to understand the mechanisms of fibrosis and develop new therapeutic strategies. Recent in-depth studies on ferroptosis have revealed a growing body of evidence that highlights the crucial role of ferroptosis in the pathophysiological process of fibrosis [93].…”

Section: Fibrosismentioning

confidence: 99%

The Road from AKI to CKD: Molecular Mechanisms and Therapeutic Targets of Ferroptosis

et al. 2023

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Acute kidney injury (AKI) is a prevalent pathological condition that is characterized by a precipitous decline in renal function. In recent years, a growing body of studies have demonstrated that renal maladaptation following AKI results in chronic kidney disease (CKD). Therefore, targeting the transition of AKI to CKD displays excellent therapeutic potential. However, the mechanism of AKI to CKD is mediated by multifactor, and there is still a lack of effective treatments. Ferroptosis, a novel nonapoptotic form of cell death, is believed to have a role in the AKI to CKD progression. In this study, we retrospectively examined the history and characteristics of ferroptosis, summarized ferroptosis’s research progress in AKI and CKD, and discussed how ferroptosis participates in regulating the pathological mechanism in the progression of AKI to CKD. Furthermore, we highlighted the limitations of present research and projected the future evolution of ferroptosis. We hope this work will provide clues for further studies of ferroptosis in AKI to CKD and contribute to the study of effective therapeutic targets to prevent the progression of kidney diseases.

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Therapeutic Implications of Ferroptosis in Renal Fibrosis

Cited by 16 publications

References 293 publications

Mechanisms of ferroptosis in chronic kidney disease

Mechanisms of ferroptosis in chronic kidney disease

Diagnostic model constructed by five EMT-related genes for renal fibrosis and reflecting the condition of immune-related cells

The Road from AKI to CKD: Molecular Mechanisms and Therapeutic Targets of Ferroptosis

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