Novel aspect of neprilysin in kidney fibrosis via ACSL4‐mediated ferroptosis of tubular epithelial cells

Lai, Weijing; Huang, Rongshuang; Wang, Bo; Shi, Min; Guo, Fan; Li, Lingzhi; Ren, Qian; Tao, Sibei; Fu, Ping; Ma, Liang

doi:10.1002/mco2.330

Cited by 9 publications

(3 citation statements)

References 36 publications

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“…Neprilysin, or MME, is a membrane metallo‐endopeptidase and its expression is elevated in kidney biopsies of patients with chronic kidney disease, which is associated with kidney fibrosis. Inhibition of neprilysin can lead to reduced levels of inflammation related markers like TNF‐α, IL‐1β and IL‐6 (Lai et al., 2023). As mentioned before, ADH7 is reduced in aniridia limbal epithelial cells and contributes to retinol oxidation.…”

Section: Discussionmentioning

confidence: 99%

Protein profiling of conjunctival impression cytology samples of aniridia subjects

Stachon,

Fecher‐Trost,

Latta

et al. 2023

Acta Ophthalmologica

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PurposeCongenital aniridia is a rare disease, which is in most cases related to PAX6 haploinsufficiency. Aniridia associated keratopathy (AAK) also belongs to ocular signs of congenital aniridia. In AAK, there is corneal epithelial thinning, corneal inflammation, vascularization and scarring. In advanced stage AAK, typically, conjunctival epithelial cells slowly replace the corneal epithelium. Based on previous results we hypothesize that alterations of the conjunctival cells in congenital aniridia may also support the corneal conjunctivalization process. The aim of this study was to identify deregulated proteins in conjunctival impression cytology samples of congenital aniridia subjects.MethodsConjunctival impression cytology samples of eight patients with congenital aniridia [age 34.5 ± 9.9 (17–51) years, 50% female] and eight healthy subjects [age 34.1 ± 11.9 (15–54) years, 50% female] were collected and analysed using mass spectrometry. Proteomic profiles were analysed in terms of molecular functions, biological processes, cellular components and pathway enrichment using the protein annotation of the evolutionary relationship (PANTHER) classification system.ResultsIn total, 3323 proteins could be verified and there were 127 deregulated proteins (p < 0.01) in congenital aniridia. From the 127 deregulated proteins (DEPs), 82 altered biological processes, 63 deregulated cellular components, 27 significantly altered molecular functions and 31 enriched signalling pathways were identified. Pathological alteration of the biological processes and molecular functions of retinol binding and retinoic acid biosynthesis, as well as lipid metabolism and apoptosis related pathways could be demonstrated.ConclusionsProtein profile of conjunctival impression cytology samples of aniridia subjects identifies alterations of retinol binding, retinoic acid biosynthesis, lipid metabolism and apoptosis related pathways. Whether these changes are directly related to PAX6 haploinsufficiency, must be investigated in further studies. These new findings offer the possibility to identify potential new drug targets.

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Section: Discussionmentioning

confidence: 99%

Protein profiling of conjunctival impression cytology samples of aniridia subjects

Stachon,

Fecher‐Trost,

Latta

et al. 2023

Acta Ophthalmologica

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“…[ 25 ] Specific inhibition of ACSL4 can significantly reduce lipid peroxidation and ferroptosis. [ 26 ] However, the ferroptosis inhibitor Ferrostain-1 (Fer-1) and vitamin E could only lower the lipid peroxide content, but not the expression of ACSL4. [ 27 , 28 ] These results suggested that ACSL4 catalyzes the initiation of lipid peroxidation and inhibition of ACSL4 could block ferroptosis from the source.…”

Section: Mechanisms Of Ferroptosismentioning

confidence: 99%

“…[ 48 ] Our studies confirmed that ACSL4-mediated ferroptosis was involved in UUO and adenine diet-induced kidney fibrosis. [ 6 , 26 ] Other reported signaling pathways include Smad3/ATF3/SLC7A11 signaling, [ 49 ] Akt/GSK-3p/Nrf2 signaling, [ 50 ] XBP1-Hrd1-Nrf2 signaling, [ 51 ] AKT/ mTOR/Nrf2 signaling, [ 52 ] TLR4/Nox4 signaling [ 53 ] and so on ( Figure 3A ).…”

Section: Kidney Fibrosismentioning

confidence: 99%

Ferroptosis in organ fibrosis: From mechanisms to therapeutic medicines

Lai,

Wang,

Huang

et al. 2024

Journal of Translational Internal Medicine

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Fibrosis occurs in many organs, and its sustained progress can lead to organ destruction and malfunction. Although numerous studies on organ fibrosis have been carried out, its underlying mechanism is largely unknown, and no ideal treatment is currently available. Ferroptosis is an iron-dependent process of programmed cell death that is characterized by lipid peroxidation. In the past decade, a growing body of evidence demonstrated the association between ferroptosis and fibrotic diseases, while targeting ferroptosis may serve as a potential therapeutic strategy. This review highlights recent advances in the crosstalk between ferroptosis and organ fibrosis, and discusses ferroptosis-targeted therapeutic approaches against fibrosis that are currently being explored.

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An inflammatory cytokine signature predicts IgA nephropathy severity and progression

Chen,

Cai

et al. 2024

MedComm

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IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, resulting in end‐stage renal disease and increased mortality rates. Prognostic biomarkers reflecting molecular mechanisms for effective IgAN management are urgently needed. Analysis of kidney single‐cell transcriptomic sequencing data demonstrated that IgAN expressed high‐expression levels of inflammatory cytokines TNFSF10, TNFSF12, CCL2, CXCL1, and CXCL12 than healthy controls (HCs). We also measured the urine proteins in 120 IgAN (57 stable and 63 progressive) and 32 HCs using the proximity extension assay (PEA), and the multivariable and least absolute shrinkage and selection operator (LASSO) logistic regression analysis both revealed that CXCL12, MCP1 were the prognostic significant variables to predict IgAN progression severity. These two proteins exhibited negative correlation with the estimated glomerular filtration rate (eGFR) and patients with higher expression levels of these two proteins had a higher probability to have poorer renal outcome. We further developed a risk index model utilizing CXCL12, MCP1, and baseline clinical indicators, which achieved an impressive area under the curve (AUC) of 0.896 for prediction of IgAN progression severity. Our study highlights the significance of the inflammatory protein biomarkers for noninvasive prediction of IgAN severity and progression, offering valuable insights for clinical management.

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Novel aspect of neprilysin in kidney fibrosis via ACSL4‐mediated ferroptosis of tubular epithelial cells

Cited by 9 publications

References 36 publications

Protein profiling of conjunctival impression cytology samples of aniridia subjects

Protein profiling of conjunctival impression cytology samples of aniridia subjects

Ferroptosis in organ fibrosis: From mechanisms to therapeutic medicines

An inflammatory cytokine signature predicts IgA nephropathy severity and progression

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