FBLN1 regulates ferroptosis in acute respiratory distress syndrome by reducing free ferrous iron by inhibiting the TGF-β/Smad pathway DOI Creative Commons
Yaping Yuan,

Youbo Wang,

Yu-Feng Yan

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(12), P. e0314750 - e0314750

Published: Dec. 13, 2024

Background Acute respiratory distress syndrome (ARDS) / acute lung injury (ALI) is a serious medical disease characterized by pulmonary dysfunction and inflammation. This study aims to determine the main molecular modules linked ARDS investigate role of Fibulin-1 (FBLN1) in regulating ferroptosis ARDS. Methods Weighted Gene Co-expression Network Analysis (WGCNA) was employed on GSE263867 dataset find key associated with ALI. Differentially expressed genes (DEGs) protein-protein interaction (PPI) networks were analyzed. MLE-12 cells treated lipopolysaccharide (LPS) induce ferroptosis. In vitro studies conducted effects FBLN1 Transforming Growth Factor Beta 1 (TGF-β) overexpression cell viability, oxidative stress markers, ferroptosis-related proteins. Results WGCNA identified turquoise module as significantly negatively correlated Five overlapping ( GRIA1 , OGN COL14A1 COL6A3 ) downregulated samples. LPS treatment induced cells, indicated increased malondialdehyde (MDA), lipid reactive oxygen species (ROS), ferrous iron (Fe 2 ⁺) levels, decreased viability glutathione (GSH) levels. partially reversed these effects. Additionally, inhibited TGF-β/Smad signaling pathway, shown TGF-β p-Smad protein exacerbated LPS-induced ferroptosis, reducing GSH counteracted this effect, suggesting antagonistic roles for Conclusion highlights critical regulator Targeting pathway modulate expression offers potential therapeutic strategy alleviate mitigate inflammatory diseases.

Language: Английский

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases DOI Creative Commons
Yumin Wang, Jing Hu, Shuang Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

Citations

77
Uridine Alleviates Sepsis-Induced Acute Lung Injury by Inhibiting Ferroptosis of Macrophage DOI Open Access

Kai Lai,

Congkuan Song,

Minglang Gao

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5093 - 5093

Published: March 7, 2023

Uridine metabolism is extensively reported to be involved in combating oxidative stress. Redox-imbalance-mediated ferroptosis plays a pivotal role sepsis-induced acute lung injury (ALI). This study aims explore the of uridine ALI and regulatory mechanism ferroptosis. The Gene Expression Omnibus (GEO) datasets including tissues lipopolysaccharides (LPS) -induced model or human blood sample sepsis were collected. In vivo vitro, LPS was injected into mice administered THP-1 cells generate inflammatory models. We identified that phosphorylase 1 (UPP1) upregulated septic samples significantly alleviated injury, inflammation, tissue iron level lipid peroxidation. Nonetheless, expression biomarkers, SLC7A11, GPX4 HO-1, upregulated, while synthesis gene (ACSL4) greatly restricted by supplementation. Moreover, pretreatment inducer (Erastin Era) weakened inhibitor (Ferrostatin-1 Fer-1) strengthened protective effects uridine. Mechanistically, inhibited macrophage activating Nrf2 signaling pathway. conclusion, dysregulation novel accelerator for supplementation may offer potential avenue ameliorating suppressing

Language: Английский

Citations

57
Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway DOI Creative Commons

Lejing Lou,

Min Wang, Jingjing He

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 9, 2023

Acute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) pomegranate intestinal flora metabolite anti-inflammatory, antioxidant, anti-aging properties. Ferroptosis critical factor in lipopolysaccharide (LPS)-induced acute (ALI). However, the link between UA ferroptosis unknown. The purpose of this research was to look into role regulating LPS-induced ALI. current study used LPS injure two models, one BEAS-2B cell model ALI mouse model. effectively alleviated compared group by lowering vivo wet/dry weight ratio, reactive oxygen species, malondialdehyde production, as well superoxide dismutase, catalase, glutathione depletion. Furthermore, increasing GPX4 SLC7A11 expression decreasing Fe2+ levels, histopathological damage, inflammatory cytokine secretion, levels can be significantly reduced. Keap1-Nrf2/HO-1 pathway upregulated UA, which inhibited ferroptosis. ML385 UA's protective effect against These findings suggested that could novel potential therapeutic target for

Language: Английский

Citations

36
Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review) DOI Creative Commons
Dickson Kofi Wiredu Ocansey, Jintao Yuan, Zhiping Wei

et al.

International Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 51(6)

Published: May 16, 2023

Ferroptosis, a novel form of regulated cell death, is characterized by the accumulation labile iron and lipid peroxidation, excessive production reactive oxygen species (ROS). Although ferroptosis lies at center crucial biological activities involving O2, polyunsaturated fatty acids (PUFAs), which are essential for proliferation growth, interaction between these molecules could also mediate toxic levels ROS peroxides, can then cause damage to cellular membranes ultimately result in death. Recent reports have indicated that participates development progression inflammatory bowel disease (IBD), offering new exploratory field may aid more in‑depth understanding pathogenesis therapeutic targets IBD. Of note, mitigation characteristic features ferroptosis, such as depleted glutathione (GSH) levels, inactivated peroxidase 4 (GPX4), elevated peroxidation overload significantly relieve This has attracted attention researches aiming examine agents inhibit IBD, including radical‑trapping antioxidants, enzyme inhibitors, chelators, protein degradation stem cell‑derived exosomes oral N‑acetylcysteine or glutathione. The present review summarizes discusses current data implicate IBD its inhibition alternate target mechanisms key mediators GSH/GPX4, PUFAs, organic peroxides discussed. relatively new, regulation exhibited promising outcomes treatment avenue

Language: Английский

Citations

35
Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome DOI Creative Commons
Yunchao Su, Rudolf Lucas, David Fulton

et al.

Chinese Medical Journal - Pulmonary and Critical Care Medicine, Journal Year: 2024, Volume and Issue: 2(2), P. 80 - 87

Published: June 1, 2024

Endothelial cells (ECs) form a semi-permeable barrier between the interior space of blood vessels and underlying tissues. Pulmonary endothelial integrity is maintained through coordinated cellular processes involving receptors, signaling molecules, junctional complexes, protein-regulated cytoskeletal reorganization. In acute lung injury (ALI) or its more severe respiratory distress syndrome (ARDS), loss secondary to dysfunction caused by pulmonary inflammation and/or infection leads edema hypoxemia. Pro-inflammatory agonists such as histamine, thrombin, bradykinin, interleukin 1β, tumor necrosis factor α, vascular growth factor, angiopoietin-2, platelet-activating well bacterial toxins reactive oxygen species, cause dynamic changes in structure, adherens junction disorganization, detachment cadherin (VE-cadherin) from actin cytoskeleton, leading an increase permeability. interactions with leukocytes, platelets, coagulation enhance inflammatory response. Moreover, infiltration associated generation pro-inflammatory cytokines during EC death, resulting further compromise structural barrier. Despite use potent antibiotics aggressive intensive care support, mortality ALI still high, because mechanisms disruption are not fully understood. this review, we summarized recent advances studies reorganization, inter-endothelial junctions, inflammation, repair ARDS, intending shed some light on potential diagnostic therapeutic targets clinical management disease.

Language: Английский

Citations

14
Regulated programmed cell death in sepsis associated acute lung injury: From pathogenesis to therapy DOI

Ruiming Deng,

Guiming Huang,

Tingting Wang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114111 - 114111

Published: Jan. 19, 2025

Language: Английский

Citations

1
Triptolide Alleviates Acute Lung Injury by Reducing Mitochondrial Dysfunction Mediated Ferroptosis Through the STAT3/p53 Pathway DOI

Jia Zhou,

Sanzhong Li,

Yuting Yang

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Ferroptosis in Pulmonary Disease and Lung Cancer: Molecular Mechanisms, Crosstalk Regulation, and Therapeutic Strategies DOI Creative Commons
Dandan Guo, Songhua Cai,

Lvdan Deng

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: Feb. 23, 2025

Ferroptosis is a distinct form of iron-dependent programmed cell death characterized primarily by intracellular iron accumulation and lipid peroxidation. Multiple cellular processes, including amino acid metabolism, various signaling pathways, autophagy, have been demonstrated to influence the induction progression ferroptosis. Recent investigations elucidated that ferroptosis plays crucial role in pathogenesis pulmonary disorders, lung injury, chronic obstructive disease, fibrosis, asthma. increasingly recognized as promising novel strategy for cancer treatment. Various immune cells within tumor microenvironment, CD8+ T cells, macrophages, regulatory natural killer dendritic shown induce modulate process through regulation metabolism pathways. Conversely, can reciprocally alter metabolic environment, leading activation or inhibition functions, thereby modulating responses. This paper reviews molecular mechanism describes discusses connection between microenvironment diseases, development prospect their interaction treatment diseases.

Language: Английский

Citations

1
Role of Ferroptosis in Regulating the Epithelial–Mesenchymal Transition in Pulmonary Fibrosis DOI Creative Commons
Hong Ling, Hong Xiao, Ting Luo

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(1), P. 163 - 163

Published: Jan. 9, 2023

Idiopathic pulmonary fibrosis is a chronic interstitial lung disease whose pathogenesis involves complex interaction of cell types and signaling pathways. Lung epithelial cells responding to repeated injury experience persistent inflammation sustained epithelial–mesenchymal transition (EMT). The persistence EMT-induced signals generates extracellular matrix accumulation, thereby causing fibrosis. Ferroptosis newly characterized iron-dependent non-apoptotic regulated death. Increased iron accumulation can increase iron-induced oxidant damage in alveolar cells. Studies have demonstrated that steady states oxidation play an important role the death regulation EMT. This review summarizes ferroptosis regulating EMT fibrosis, aiming provide new idea for prevention treatment this disease.

Language: Английский

Citations

22
Deletion of BACH1 alleviates ferroptosis and protects against LPS-triggered acute lung injury by activating Nrf2/HO-1 signaling pathway DOI
Ruixuan Wang,

Xing Gu,

Si-xue Zhang

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2023, Volume and Issue: 644, P. 8 - 14

Published: Jan. 3, 2023

Language: Английский

Citations

18