Tangeretin alleviates LPS-induced acute lung injury by inhibiting ferroptosis of macrophage via Nrf2 pathways
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1062399 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27470049_1.fastq.gz | Fastqsanger.gz | |||
| SRR27470049_2.fastq.gz | Fastqsanger.gz | |||
| SRR27470050_1.fastq.gz | Fastqsanger.gz | |||
| SRR27470050_2.fastq.gz | Fastqsanger.gz | |||
| SRR27470051_1.fastq.gz | Fastqsanger.gz |
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Project description:Sepsis-induced acute lung injury (ALI) is a severe clinical condition with a high mortality rate. Tangeretin, widely found in citrus fruits, has been reported to exert antioxidant and anti-inflammatory properties. However, whether Tangeretin protects against sepsis-induced ALI and the potential mechanisms remain unclear.We established ALI model via intraperitoneally injected with 5 mg/kg lipopolysaccharides (LPS) for 12 h. Tangeretin was applied intraperitoneally 30 min before LPS treatment. The lung tissue samples from both the LPS and LPS + TAN groups were subjected to RNA sequencing analysis, conducted by OE Biotech Co., Ltd. (Shanghai, China). We performed differential gene expression analysis using RNA-seq data between LPS and LPS/Tangeretin group.GSEA analysis between LPS and LPS/Tangeretin group showed that IL6_JAK_STAT3_SIGNALING, INFLAMMATORY_RESPONSE, TNFA_SIGNALING_VIA_NFKB were significantly enriched (Fig.3C-E). These results identified the anti-inflammatory effect of Tangeretin against sepsis-induced ALI.
2024-01-20 | GSE252755 | GEO
Project description:Acute kidney injury (AKI) is a common and life-threatening condition associated with cell death, where ferroptosis plays a critical role. Chemerin, primarily produced in white adipose tissue, has multiple biological functions in renal pathophysiology. However, to date, whether and how chemerin regulates the progression of AKI remain unclear. Here, we found that chemerin expression was reduced in both AKI model mice and cells. Similarly, serum chemerin levels were also decreased in AKI patients. The administration of recombinant chemerin improves renal function in ischemia-reperfusion (I/R) model mice. Chemerin significantly attenuates ferroptosis in kidneys. In TCMK-1 cells, chemerin knockdown further aggravates ferroptosis. Mechanistically, chemerin activates AMP-activated protein kinase (AMPK), which induces the phosphorylation of nuclear factor erythroid 2-related factor 2 (NRF2) in renal tubular cells. Subsequently, NRF2 translocates into the nucleus, where it stimulates the expression of cystine/glutamate antiporter solute carrier (SLC7A11). As a result, cystine uptake and glutathione (GSH) biosynthesis in renal tubular cells were increased, which confers cells with higher capacity against ferroptosis. Overall, our findings indicate that chemerin plays a protective role in AKI by repressing ferroptosis in renal tubular cells, which is likely due to the activation in the AMPK/NRF2/SLC7A11 axis.
2024-12-01 | GSE283126 | GEO
Project description:Here, through genome-wide CRISPR-Cas9 screenings, we identified GAS41, a well-known histone reader as a major repressor for ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recognizing the H3K27-acetylation (H3K27-ac) marker, GAS41 is recruited to the SLC7A11 promoter independent of NRF2 binding. Notably, by bridging the interaction between NRF2 and the H3K27-ac marker, GAS41 acts as an anchor for NRF2 on chromatin in a promoter-specific manner for transcriptional activation. Moreover, the GAS41-mediated effect on ferroptosis contributes significantly to its oncogenic role in vivo. These data demonstrate that GAS41 is an important target for modulating tumor growth through ferroptosis. Our study reveals a previously unanticipated mechanism for GAS41-mediated regulation in transcription by anchoring NRF2 on chromatin and provides a model that the DNA binding activity on chromatin by transcriptional factors (NRF2) can be directly regulated by histone markers (H3K27-ac).
2024-03-01 | GSE256462 | GEO
Project description:Cisplatin resistance is a major cause of poor prognosis in non-small cell lung cancer (NSCLC). Cisplatin-induced lung cancer cell death is associated with ferroptosis, a type of recently identified programmed cell death. Nrf2 is a critical component of the antioxidant system, and its pro-tumorigenic activity in lung cancer has been extensively studied. However, the role of Nrf2 in cisplatin-induced ferroptosis and drug resistance remains elusive. Here, we demonstrate that cisplatin treatment induced ferroptosis in parental A549 lung adenocarcinoma cells, and that this effect was significantly reduced in cisplatin-resistant A549/DDP cells. Knocking down Nrf2 sensitized A549/DDP cells to cisplatin-induced cytotoxicity by enhancing ferroptosis. Moreover, we demonstrated that Nrf2 promotes the expression of HMOX1, and the Nrf2-HMOX1 pathway is critical in mediating the anti-ferroptotic function. Additionally, immunohistochemical analysis of NSCLC specimens indicated that the Nrf2 expression was correlated with HMOX1, and high levels of Nrf2 and HMOX1 were associated with poor patient survival. These findings suggest that the HMOX1-Nrf2 pathway significantly influences treatment outcomes in NSCLC. Ultimately, we demonstrated that treatment with Nrf2 inhibitor ML385 promoted ferroptosis by inhibiting the Nrf2-HMOX1 pathway, restoring cisplatin sensitivity in drug-resistant cells. Our findings provide insights into the mechanism underlying cisplatin resistance and suggests that targeting the Nrf2-HMOX1 pathway enhances cisplatin-induced ferroptosis and improves NSCLC treatment outcomes.
2025-06-17 | GSE288129 | GEO
Project description:Background/Objectives: Ferroptosis, an iron-dependent form of cell death, shows promise as a target for therapy-resistant cancers that exhibit increased iron metabolism. Ferroptosis is primarily characterised by lipid peroxidation within cell membranes. However, many cancers evade ferroptosis by upregulation of specialised ferroptosis defence mechanisms. This study investigates ferroptosis susceptibility in Tuberous Sclerosis Complex (TSC) cell models, and ovarian and breast cancer cell lines to identify ferroptosis resistance mechanisms and therapeutic targets. Methods: We assessed ferroptosis susceptibility using the ferroptosis inducers, RSL3 and erastin. We explored ferroptosis resistance genes using inhibitors of NRF2 (ML385) and FSP1 (iFSP1). RNA-sequencing was conducted to identify dysregulated ferroptosis resistance genes and to better characterise NRF2 target genes. RNA sequencing was also performed to identify gene expression after treatment with pro-ferroptotic iron-oxide nanoparticles. Results: TSC2-deficient cells exhibited resistance to RSL3 and erastin-induced ferroptosis, which correlated with increased ferroptosis defence gene expression, including NRF2 and downstream targets. NRF2 inhibition re-sensitised TSC2-deficient cells to ferroptosis, confirming its protective role. However, FSP1 inhibition did not re-sensitise TSC2-deficient angiomyolipoma kidney tumor cells to RSL3. In contrast, FSP1 knockdown significantly enhanced ferroptosis sensitivity in ovarian (PEO1, PEO4, OVCAR3) and breast (MDA-MB-436) cancer cell lines. Notably, in MDA-MB-436 cells, FSP1 knockdown was more effective than NRF2 inhibition in reversing ferroptosis resistance. Conclusions: Our findings highlight NRF2 and FSP1 as key regulators of ferroptosis resistance in TSC2-deficient and cancer cells. However, the differential efficacy of targeting these pathways suggests that patient stratification may be necessary for optimal therapeutic strategies. Targeting NRF2 and FSP1 could enhance ferroptosis susceptibility, offering a potential therapeutic approach for ferroptosis resistance cancers.
2025-07-14 | GSE300960 | GEO
Project description:Chemerin attenuates acute kidney injury by inhibiting ferroptosis via the AMPK/NRF2/SLC7A11 axis
| PRJNA1192208 | ENA
Project description:Ferroptosis plays an important role in inflammation and oxidative stress. Whether ferroptosis is involved in the inflammation of vascular endothelial cells and its regulation mechanism remains unclear. We estimated the correlation between serum iron ion levels and the inflammation index of 33 patients with arteriosclerosis. In vitro, HUVECs with or without ferrostatin-1 were exposed to Lipopolysaccharide. Corresponding cell models to verify the target signaling pathway. The results showed that serum iron ion levels had a significant positive correlation with N ratio, N/L, LDL level, and LDL/HDL (P < 0.05), and a negative correlation with L ratio (P < 0.05) in the arteriosclerosis patients. In vitro, ferroptosis is involved in HUVECs inflammation. Ferrostatin-1 can rescue LPS-induced HUVECs inflammation by decreasing HMGB1/IL-6/TNF-α expression. Nrf2 high expression could protect HUVECs against ferroptosis by activating the GPX4/GSH system, inhibiting ferritinophagy, and alleviating inflammation in HUVECs by inhibiting HMGB1/IL-6/TNF-α expression. It also found that Nrf2 is a key adaptive regulatory factor in the oxidative damage of HUVECs induced by NOX4 activation. These findings indicated that ferroptosis contributed to the pathogenesis of vascular endothelial cell damage by mediating endothelial cell inflammation. Nrf2-mediated redox balance in vascular inflammation may be a therapeutic strategy in vascular diseases.
| S-EPMC10858270 | biostudies-literature
Project description:Per2 deficiency in microglia alleviates motor dysfunction by inhibiting ferroptosis in spinal cord injury
| PRJNA1294408 | ENA
Project description:Microglia are more susceptible to ferroptosis compared to neurons and astrocytes, which may compromise their phagocytic and clearance capabilities of α-synuclein (α-syn) in Parkinson’s disease (PD). While the beneficial effects of physical exercise (PE) on reducing α-syn deposition in PD have been highlighted, the role of PE in modulating microglial ferroptosis remains unclear. This study focuses on the impact of exercise on inhibiting microglial ferroptosis and mitigating α-syn accumulation. We demonstrate that voluntary exercise effectively inhibits microglial ferroptosis. Mechanistically, PE-induced upregulation of SLC7A11 inhibits microglial ferroptosis by suppressing ALOX12, thereby enhancing microglial phagocytosis and clearance of α-syn, which is paralleled by improvements in neurological function in PD mice. Collectively, these findings not only underscore the critical role of microglial ferroptosis in the pathological progression of PD but also elucidate the molecular mechanism by which PE attenuates microglial ferroptosis via the SLC7A11/ALOX12 axis.
2025-09-29 | GSE309457 | GEO
Project description:SCD had hemolysis with elevated levels of heme and iron, which induced ferroptosis. Here, we found Nrf2 knockout in SCD mice accumulated the levels of the metabolite L-2-hydroxyglutarate (L2HG), which impaired ferroptosis stress response to exacerbate SCD symptom. Mechanistically, L2HG was found to regulate the expression of genes involved in the iron and heme metabolism via histone epigenetic hypermethylation. Our findings indicate an important role of Nrf2/L2HG in SCD for ferroptosis response.
2021-11-19 | GSE188695 | GEO