The role of epithelial cells in fibrosis: Mechanisms and treatment

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107144 - 107144

Published: March 13, 2024

Fibrosis is a pathological process that affects multiple organs and considered one of the major causes morbidity mortality in diseases, resulting an enormous disease burden. Current studies have focused on fibroblasts myofibroblasts, which directly lead to imbalance generation degradation extracellular matrix (ECM). In recent years, increasing number role epithelial cells fibrosis. some cases, are first exposed external physicochemical stimuli may drive collagen accumulation mesenchyme. other source stimulation mainly immune cytokines, similarly altered process. this review, we will focus dynamic alterations involved after injury during fibrogenesis, discuss association among them, summarize therapies targeting changed cells. Especially, mesenchymal transition (EMT) key central step, closely linked biological behaviors. Meanwhile, think disruption barrier, cell death basal stem populations stemness fibrosis not appreciated. We believe targeted can prevent progress fibrosis, but reverse it. The provide wonderful preventive delaying action.

Language: Английский

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Muribaculum intestinale-derived 3-hydroxybutyric acid from Heterophyllin B attenuated pulmonary fibrosis through IDO1-mediated ferroptosis

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107587 - 107587

Published: Jan. 6, 2025

Pulmonary fibrosis (PF) is a fatal disease with increasing incidence, poor prognosis, and unclear pathogenesis. Our previous research demonstrated the beneficial effects of natural cyclopeptide Heterophyllin B (HB) in PF. However, precise mechanism by which HB exerts its PF remains unclear. study revealed HB's alleviating symptoms restoring intestinal mucosal barrier. Subsequently, microbiota-dependent antifibrotic efficacy was verified using various delivery routes, antibiotic treatments, faecal microbiota transplantation. Functionally, 16S rRNA sequencing, untargeted metabolomics, co-incubation experiments that primarily contingent on enrichment Muribaculum intestinale metabolite, 3-hydroxybutyric acid. Mechanistically, indoleamine 2,3- dioxygenase 1 (IDO1)-mediated ferroptosis identified as pivotal process initiating PF, anti-fibrotic relies suppressing IDO1-mediated ferroptosis. Conversely, IDO1 deficiency alleviated bleomycin-induced mice. Coincidentally, both overexpression were observed pulmonary tissue patients idiopathic Collectively, this alleviates eliminating microecology metabolism highlights feasibility targeting for treatment.

Language: Английский

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Ferroptosis in Pulmonary Disease and Lung Cancer: Molecular Mechanisms, Crosstalk Regulation, and Therapeutic Strategies

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

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Role of Ferroptosis in Regulating the Epithelial–Mesenchymal Transition in Pulmonary Fibrosis

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

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ACSL4 inhibition prevents macrophage ferroptosis and alleviates fibrosis in bleomycin-induced systemic sclerosis model

Arthritis Research & Therapy, Journal Year: 2023, Volume and Issue: 25(1)

Published: Oct. 26, 2023

Systemic sclerosis (SSc), with unclear pathophysiology, is a paradigmatic rheumatic disease of immunity dysfunction-driven multi-organ inflammation and ultimate fibrosis. Pathogenesis breakthroughs are urgently needed for available treatments halting its unremitting stiffness. This study aims to investigate whether ferroptosis can regulate the progressive SSc fibrosis.In vivo, bleomycin (BLM)-induced mice model was subjected detection using western blotting, malondialdehyde (MDA), glutathione (GSH) assays. Pharmacological inhibitor acyl-CoA synthetase long-chain family member 4 (ACSL4) utilized explore potential therapeutic effects fibrosis, from histological, biochemical, molecular analyses. In vitro, bone marrow-derived macrophages (BMDM) were activated into inflammatory phenotype then relationship evaluated between activation level sensitivity in lipopolysaccharide (LPS) incubation gradient concentrations. The calpain/ACSL4 axis analyzed after calpain knockdown or over-expression Raw264.7.Both skin lung tissue present enhanced ACSL4 expression, while inhibition effectively halted fibrosis progressing provides protection milieu. Meanwhile, positive regulation LPS-induced macrophage activity be observed. After knockdown, both expression decreased, renders ACSL4-envoking condition. Also, pharmacological reduced aptitude mice.ACSL4 induces aggravate progressing. upregulators calpains may targets BLM SSc.

Language: Английский

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Molecular mechanism of interleukin-17A regulating airway epithelial cell ferroptosis based on allergic asthma airway inflammation

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102970 - 102970

Published: Nov. 22, 2023

Interleukin-17A (IL-17A) levels are elevated in patients with asthma. Ferroptosis has been identified as the non-apoptotic cell death type associated Data regarding relation of ferroptosis asthma and effect IL-17A on modulating remain largely unclear. The present work focused investigating role allergic asthma-related its molecular mechanisms using public datasets, clinical samples, human bronchial epithelial cells, an mouse model. We found that was significantly upregulated within serum cases. Adding increased cells (BEAS-2B). In ovalbumin (OVA)-induced asthmatic mice, regulated activated lipid peroxidation induced ferroptosis, whereas knockdown effectively inhibited vivo by protection airway via xCT-GSH-GPX4 antioxidant system reduced inflammation. Mouse mRNA sequencing results indicated tumor necrosis factor (TNF) pathway differential KEGG OVA group compared to healthy controls knockout group. further used N-acetylcysteine (TNF inhibitor) inhibit TNF signaling pathway, which protect BEAS-2B from damage. Our findings reveal a novel mechanism for suppression may represent new strategy use inhibitors against

Language: Английский

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Protective efficacy of Schizandrin B on ameliorating nephrolithiasis via regulating GSK3β/Nrf2 signaling-mediated ferroptosis in vivo and in vitro

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 117, P. 110042 - 110042

Published: March 20, 2023

Language: Английский

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Ferroptosis contributes to endometrial fibrosis in intrauterine adhesions

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 205, P. 151 - 162

Published: June 10, 2023

Language: Английский

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Ferroptosis as a Potential Therapeutic Target for Reducing Inflammation and Corneal Scarring in Bacterial Keratitis

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(2), P. 29 - 29

Published: Feb. 21, 2024

Purpose: Bacterial keratitis (BK) is a serious ocular infection that can cause severe inflammation and corneal scarring, leading to vision loss. In this study, we aimed investigate the involvement of ferroptosis in pathogenesis BK. Methods: Transcriptome analysis was performed evaluate ferroptosis-related gene expression human BK corneas. Subsequently, mouse models Pseudomonas aeruginosa stromal stem cells (CSSCs) were validated. The mice treated with levofloxacin (LEV) or combined ferrostatin-1 (LEV+Fer-1). CSSCs lipopolysaccharide (LPS) LPS Fer-1. Inflammatory cytokines, α-SMA, regulators evaluated by RT-qPCR, immunostaining, Western blot. Iron reactive oxygen species (ROS) measured. Results: revealed significant alterations genes models, group LEV+Fer-1 exhibited reduced inflammatory cytokines (MPO, TNF-α, IFN-γ), decreased scarring α-SMA expression, lower Fe3+ compared LEV groups. Notably, showed elevated GPX4 SLC7A11 contrast group. vitro, Fer-1 treatment effectively restored ROS, Fe2+, GPX4, induced CSSCs. Conclusions: Ferroptosis plays crucial role inhibition holds promise for mitigating inflammation, reducing ultimately enhancing prognosis Consequently, study provides potential target innovative therapeutic strategies BK, which immense transform

Language: Английский

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Ferroptosis in Glaucoma: A Promising Avenue for Therapy

Advanced Biology, Journal Year: 2024, Volume and Issue: 8(5)

Published: Feb. 27, 2024

Abstract Glaucoma, a blind‐leading disease largely since chronic pathological intraocular high pressure (ph‐IOP). Hitherto, it is reckoned incurable for irreversible neural damage and challenges in managing IOP. Thus, significant to develop neuroprotective strategies. Ferroptosis, initially identified as an iron‐dependent regulated death that triggers Fenton reactions culminates lipid peroxidation (LPO), has emerged focal point multiple tumors neurodegenerative diseases. Researches show iron homeostasis play critical roles the optic nerve (ON) retinal ganglion cells (RGCs), suggesting targeted treatments could be effective. In glaucoma, apart from lesions, disrupted metal balance increased oxidative stress trabecular meshwork (TM) are observed. These disturbances lead extracellular matrix excretion disorders, known sclerotic mechanisms, resulting refractory blockages. Importantly, stress, downstream effect of ferroptosis, also key factor cell senescence. It plays crucial role both etiology risk glaucoma. Moreover, ferroptosis induces non‐infectious inflammation, which exacerbate glaucomatous injury. Therefore, relevance glaucoma extensive multifaceted. this review, study delves into current understanding mechanisms aiming provide clues inform clinical therapeutic practices.

Language: Английский

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