Kidney tubular epithelial cell ferroptosis links glomerular injury to tubulointerstitial pathology in lupus nephritis

Alli, Abdel A.; Desai, Dhruv; Elshika, Ahmed; Conrad, Marcus; Proneth, Bettina; Clapp, William L.; Atkinson, Carl; Segal, Mark S.; Searcy, Louis A.; Denslow, Nancy D.; Bolisetty, Subhashini; Mehrad, Borna; Morel, Laurence; Scindia, Yogesh

doi:10.1016/j.clim.2022.109213

Cited by 40 publications

(21 citation statements)

References 67 publications

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“…Additionally, ferroptosis has led to advancements in the study of lupus nephritis (LN). Evidence suggests that kidney tubular epithelial cell ferroptosis is related to glomerular damage in tubulointerstitial disease in LN [57]. The kidneys of LN patients and mice demonstrated increased lipid peroxidation, particularly in the tubular segments, as well as an increase in Acyl-CoA synthetase long-chain family member 4, a pro-ferroptosis enzyme [57].…”

Section: Ferroptosis and Ckdmentioning

confidence: 99%

“…Evidence suggests that kidney tubular epithelial cell ferroptosis is related to glomerular damage in tubulointerstitial disease in LN [57]. The kidneys of LN patients and mice demonstrated increased lipid peroxidation, particularly in the tubular segments, as well as an increase in Acyl-CoA synthetase long-chain family member 4, a pro-ferroptosis enzyme [57]. Serum from LN patients made human proximal tubular cells susceptible to ferroptosis, which was reduced by Liproxstatin-2, a new ferroptosis inhibitor [57].…”

Section: Ferroptosis and Kidney Diseasesmentioning

confidence: 99%

“…The kidneys of LN patients and mice demonstrated increased lipid peroxidation, particularly in the tubular segments, as well as an increase in Acyl-CoA synthetase long-chain family member 4, a pro-ferroptosis enzyme [57]. Serum from LN patients made human proximal tubular cells susceptible to ferroptosis, which was reduced by Liproxstatin-2, a new ferroptosis inhibitor [57]. These findings pointed to intrarenal ferroptosis as a pathogenic characteristic and contributor to tubular injury in human and mouse LN [57].…”

Section: Ferroptosis and Kidney Diseasesmentioning

confidence: 99%

“…Serum from LN patients made human proximal tubular cells susceptible to ferroptosis, which was reduced by Liproxstatin-2, a new ferroptosis inhibitor [57]. These findings pointed to intrarenal ferroptosis as a pathogenic characteristic and contributor to tubular injury in human and mouse LN [57]. Recent advances in molecular markers of the glomerulus and tubule interstitium in LN suggested that LTF, CYBB, CCL5, G0S2, and AKR1C1, particularly CYBB, could be useful biomarkers of ferroptosis in LN [58].…”

Section: Ferroptosis and Kidney Diseasesmentioning

confidence: 99%

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Novel Insight into Ferroptosis in Kidney Diseases

Liu¹,

Liu²,

Zhou³

et al. 2023

Am J Nephrol

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Background: Various kidney diseases such as acute kidney injury, chronic kidney disease, polycystic kidney disease, renal cancer, and kidney stones, are an important part of the global burden, bringing a huge economic burden to people around the world. Ferroptosis is a type of nonapoptotic iron-dependent cell death caused by the excess of iron-dependent lipid peroxides and accompanied by abnormal iron metabolism and oxidative stress. Over the past few decades, several studies have shown that ferroptosis is associated with many types of kidney diseases. Studying the mechanism of ferroptosis and related agonists and inhibitors may provide new ideas and directions for the treatment of various kidney diseases. Summary: In this review, we discuss the differences between ferroptosis and other types of cell death such as apoptosis, necroptosis, pyroptosis, cuprotosis, pathophysiological features of the kidney, and ferroptosis-induced kidney injury. We also provide an overview of the molecular mechanisms involved in ferroptosis and events that lead to ferroptosis. Furthermore, we summarize the possible clinical applications of this mechanism among various kidney diseases. Key Message: The current research suggests that future therapeutic efforts to treat kidney ailments would benefit from a focus on ferroptosis.

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Section: Ferroptosis and Ckdmentioning

confidence: 99%

Section: Ferroptosis and Kidney Diseasesmentioning

confidence: 99%

Section: Ferroptosis and Kidney Diseasesmentioning

confidence: 99%

Section: Ferroptosis and Kidney Diseasesmentioning

confidence: 99%

See 2 more Smart Citations

Novel Insight into Ferroptosis in Kidney Diseases

Liu¹,

Liu²,

Zhou³

et al. 2023

Am J Nephrol

View full text Add to dashboard Cite

show abstract

“…Additionally, it involves remarkable morphological changes in mitochondria, which include reduction of mitochondrial volume and cristae, increased membrane density and disruption to the mitochondrial membrane structure [ 13 , 14 ]. Ferroptosis is involved in non-neoplastic and neoplastic diseases [ 15 , 16 , 17 ]. A recent study suggested that ferroptosis was decreased in the synovium and synovial fibroblasts (SFs) in RA patients, and glycine alleviated disease progression in collagen-induced arthritis (CIA) mice by increasing ferroptosis [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis-Related Molecular Clusters and Diagnostic Model in Rheumatoid Arthritis

Xie

Chen

2023

IJMS

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Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis, joint damage and deformity. A newly described type of cell death, ferroptosis, has an important role in the pathogenesis of RA. However, the heterogeneity of ferroptosis and its association with the immune microenvironment in RA remain unknown. Synovial tissue samples from 154 RA patients and 32 healthy controls (HCs) were obtained from the Gene Expression Omnibus database. Twelve of twenty-six ferroptosis-related genes (FRGs) were differentially expressed between RA patients and HCs. Furthermore, the patterns of correlation among the FRGs were significantly different between the RA and HC groups. RA patients were classified into two distinct ferroptosis-related clusters, of which cluster 1 had a higher abundance of activated immune cells and a corresponding lower ferroptosis score. Enrichment analysis suggested that tumor necrosis factor-α signaling via nuclear factor-κB was upregulated in cluster 1. RA patients in cluster 1 responded better to anti-tumor necrosis factor (anti-TNF) therapy, which was verified by the GSE 198520 dataset. A diagnostic model to identify RA subtypes and immunity was constructed and verified, in which the area under the curve values in the training (70%) and validation (30%) cohorts were 0.849 and 0.810, respectively. This study demonstrated that there were two ferroptosis clusters in RA synovium that exhibited distinct immune profiles and ferroptosis sensitivity. Additionally, a gene scoring system was constructed to classify individual RA patients.

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The non‐enzymatic oxidation of phosphatidylethanolamine and phosphatidylserine and their intriguing roles in inflammation dynamics and diseases

Santos,

Melo,

Maurício

et al. 2024

FEBS Letters

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Phosphatidylethanolamine (PE) and phosphatidylserine (PS), along with phosphatidylcholine (PC), are key phospholipids (PL) in cell membranes and lipoproteins, prone to oxidative modifications. Their oxidized forms, OxPE and OxPS, play significant roles in inflammation and immune response. This review explores their structural oxidative changes under non‐enzymatic conditions and their roles in physiological and pathological contexts, influencing inflammation, and immunity. Specific oxidations of PE and PS significantly alter their physicochemical properties, leading to enhanced biological functions, reduced activity, or inactivation. OxPE may show pro‐inflammatory actions, similar to well‐documented OxPC, while the OxPS pro‐inflammatory effects are less noted. However, OxPS and OxPE have also shown an antagonistic effect against lipopolysaccharides (LPS), suggesting a protective role against exacerbated immune responses, similar to OxPC. Further research is needed to deepen our understanding of these less‐studied OxPL classes. The role of OxPE and OxPS in disease pathogenesis remains largely unexplored, with limited studies linking them to Alzheimer's disease, diabetes, rheumatoid arthritis, traumatic brain injury, and skin inflammation. These findings highlight the potential of OxPE and OxPS as biomarkers for disease diagnosis, monitoring, and therapeutic targeting.

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Kidney tubular epithelial cell ferroptosis links glomerular injury to tubulointerstitial pathology in lupus nephritis

Cited by 40 publications

References 67 publications

Novel Insight into Ferroptosis in Kidney Diseases

Novel Insight into Ferroptosis in Kidney Diseases

Ferroptosis-Related Molecular Clusters and Diagnostic Model in Rheumatoid Arthritis

The non‐enzymatic oxidation of phosphatidylethanolamine and phosphatidylserine and their intriguing roles in inflammation dynamics and diseases

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