Bronchial Asthma, Airway Remodeling and Lung Fibrosis as Successive Steps of One Process

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16042 - 16042

Опубликована: Ноя. 7, 2023

Bronchial asthma is a heterogeneous disease characterized by persistent respiratory system inflammation, airway hyperreactivity, and airflow obstruction. Airway remodeling, defined as changes in wall structure such extensive epithelial damage, smooth muscle hypertrophy, collagen deposition, subepithelial fibrosis, key feature of asthma. Lung fibrosis common occurrence the pathogenesis fatal long-term asthma, it associated with severity resistance to therapy. It can thus be regarded an irreversible consequence asthma-induced inflammation remodeling. Asthma heterogeneity presents several diagnostic challenges, particularly distinguishing between chronic other pulmonary diseases disruption normal lung architecture functions, obstructive disease. The search for instruments that predict development structural lungs, components remodeling difficult. To overcome these significant efforts are being directed toward discovery investigation molecular characteristics biomarkers capable different types well disorders similar characteristics. main features bronchial etiology, pathogenesis, morphological asthma-associated successive stages one process will discussed this review. most murine models progression post-asthmatic also covered. mechanisms cellular players asthmatic described systematized review intended help new markers promising therapeutic targets prediction

Язык: Английский

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3D in vitro hydrogel models to study the human lung extracellular matrix and fibroblast function

Respiratory Research, Год журнала: 2023, Номер 24(1)

Опубликована: Окт. 5, 2023

The pulmonary extracellular matrix (ECM) is a macromolecular structure that provides mechanical support, stability and elastic recoil for different cells including the lung fibroblasts. ECM plays an important role in development, remodeling, repair, maintenance of tissue homeostasis. Biomechanical biochemical signals produced by regulate phenotype function various fibroblasts lungs. Fibroblasts are structural responsible production repair proteins (e.g., collagen fibronectin). During injury chronic diseases such as asthma, idiopathic fibrosis (IPF) obstructive disease (COPD), abnormal feedback between altered disrupts homeostasis leads to vicious cycle fibrotic changes resulting remodeling. In line with this, using 3D hydrogel culture models embedded have enabled assessment mechanisms involved driving defective (fibrotic) fibroblast lung's environment. this review, we provide summary studies used these assess regulation on health respiratory disease.

Язык: Английский

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Dressed in Collagen: 2D and 3D Cardiac Fibrosis Models

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3038 - 3038

Опубликована: Март 26, 2025

Cardiovascular diseases (CVD), the leading cause of death worldwide, and their strong association with fibrosis highlight pressing need for innovative antifibrotic therapies. In vitro models have emerged as valuable tools replicating cardiac 'in a dish', facilitating study disease mechanisms serving platforms drug testing development. These in systems encompass 2D 3D models, each its own limitations advantages. offer high reproducibility, cost-effectiveness, high-throughput capabilities, but they oversimplify complex fibrotic environment. On other hand, provide greater biological relevance are more complex, harder to reproduce, less suited screening. The choice model depends on specific research question stage Despite significant progress, challenges remain, including integration immune cells optimizing scalability throughput highly biomimetic systems. Herein, we review recent focus shared characteristics remaining challenges, explore how organs could inspire novel approaches research, showcasing potential strategies that be adapted refine myocardial models.

Язык: Английский

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Establishing a 3D Vascularized Tri‐Culture Model of the Human Airways via a Digital Light Processing Bioprinter

Biotechnology and Bioengineering, Год журнала: 2025, Номер unknown

Опубликована: Апрель 29, 2025

ABSTRACT The rise in chronic lung diseases globally and the corresponding lag drug discovery this field highlights need for In Vitro models closely mimicking Vivo tissue. Efforts to date have largely focused on coculture models, often neglecting pulmonary vasculature's role physiology lacking perfusability. To address gap, we utilized digital light processing bioprinting establish a complex three‐dimensional (3D) vascularized tri‐culture airway model. Models were generated using photopolymerizable bioink consisting of 80% polyethylene glycol diacrylate (PEGDA) 20% gelatin methacrylate (GelMa) printed LUMENX+ bioprinter. Stiffness, diffusivity, gel expansion characterized. with MRC‐5 fibroblasts embedded hydrogels, while EA.hy926 endothelial cells 1HAEo‐ epithelial seeded luminal surface apical domain, respectively. Endothelialization was achieved by coating lumens matrix proteins, followed perfusion‐based cell seeding uniform distribution via rotating Structural characterization, including immunofluorescence imaging, lactate dehydrogenase (LDH) viability, interleukin‐6 interleukin‐8 quantification performed following cigarette smoke extract (CSE) exposure. PEGDA/GelMa 80:20 hydrogels had Young's modulus 10.7 kPa, expanded 101.5% volume 107% weight after 24 h phosphate‐buffered saline, turned completely blue 12 exposure 0.1% methylene blue. Immunofluorescence staining revealed an intact layer demonstrated E‐cadherin expression. Lung retained their spindle shape dendritic extensions as shown F‐actin staining. Propidium iodide 80‐90% viability. Cigarette significantly increased IL‐6 IL‐8 release, but not LDH release. A multiplex assay distinct immune mediator profiles clustering between co‐cultures tri‐cultures at baseline, underscoring differences intercellular communication. This study successfully engineered characterized 3D bioprinted model that mimics human airways. is adaptable future studies incorporating additional types, primary cells, or modified designs protocols.

Язык: Английский

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The role of fibroblast-neutrophil crosstalk in the pathogenesis of inflammatory diseases: a multi-tissue perspective

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 23, 2025

Neutrophil-fibroblast crosstalk drives inflammatory pathology across organ systems through both shared and tissue-specific mechanisms. This review synthesizes evidence from skin, lung, gut, cardiovascular, joint, sinus, oral diseases, revealing conserved molecular pathways where fibroblasts secrete chemokines (CXCL1/8/12) to recruit neutrophils, which, in turn, release neutrophil extracellular traps (NETs), elastase, cytokines modulate fibroblast function. Additionally, we identify critical differences, including the predominance of IL-36 signaling COPD, IL-17-carrying NETs systemic lupus erythematosus (SLE) pulmonary fibrosis, specialized subpopulations, such as IDO1+ cells CRSwNP TNFRSF21+ periodontitis. Translational insights highlight therapeutic potential targeting IL-17, NETs, though risks necessitate precision strategies. Future efforts should focus on developing precision-targeted interventions that address organ-specific mechanisms overcome treatment resistance disorders.

Язык: Английский

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Ιnterleukin-17A-Enriched Neutrophil Extracellular Traps Promote Immunofibrotic Aspects of Childhood Asthma Exacerbation

Biomedicines, Год журнала: 2023, Номер 11(8), С. 2104 - 2104

Опубликована: Июль 26, 2023

Childhood asthma is a chronic inflammatory airway disorder that can drive tissue remodeling. Neutrophils are amongst the most prominent cells contributing to disease manifestations and may exert potent role in progression of inflammation fibrosis. However, their exacerbation still understudied. Here, we investigate association between neutrophil extracellular traps (NETs) lung fibroblasts childhood pathophysiology using serum samples from pediatric patients during exacerbation. Cell-based assays NETs/human fetal fibroblast co-cultures were deployed. Increased levels NETs interleukin (IL)-17A detected sera children The vitro stimulation control neutrophils resulted IL-17A-enriched NET formation. subsequent co-incubation with vitro-generated led acquire pre-fibrotic phenotype, as assessed via enhanced CCN2 expression, migratory/healing capacity, collagen release. These data uncover important pathogenic NET/IL-17A axis exacerbation, linking dysfunction

Язык: Английский

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In vitro co-culture studies and the crucial role of fibroblast-immune cell crosstalk in IPF pathogenesis

Respiratory Research, Год журнала: 2023, Номер 24(1)

Опубликована: Ноя. 27, 2023

Язык: Английский

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Deciphering metabolic crosstalk in context: lessons from inflammatory diseases

Molecular Oncology, Год журнала: 2024, Номер 18(7), С. 1759 - 1776

Опубликована: Янв. 26, 2024

Metabolism plays a crucial role in regulating the function of immune cells both health and disease, with altered metabolism contributing to pathogenesis cancer many inflammatory diseases. The local microenvironment has profound impact on cells. Therefore, immunological metabolic heterogeneity as well spatial organization tissues should be taken into account when studying immunometabolism. Here, we highlight challenges investigating communication. Additionally, review capabilities limitations current technologies for inflamed microenvironments, including single-cell omics techniques, flow cytometry-based methods (Met-Flow, energetic by profiling translation inhibition (SCENITH)), cytometry time flight (CyTOF), cellular indexing transcriptomes epitopes sequencing (CITE-Seq), mass spectrometry imaging. Considering importance diseased states, also discuss applications metabolomics clinical research, some hurdles overcome implement these techniques standard practice. Finally, provide flowchart assist scientists designing effective strategies unravel immunometabolism disease-relevant contexts.

Язык: Английский

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In vitro and in vivo protective potential of quercetin-3-glucuronide against lipopolysaccharide-induced pulmonary injury through dual activation of nuclear factor-erythroid 2 related factor 2 and autophagy

Archives of Toxicology, Год журнала: 2024, Номер 98(5), С. 1415 - 1436

Опубликована: Март 4, 2024

Язык: Английский

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Epithelial-fibroblast interactions in IPF: Lessons from in vitro co-culture studies

Differentiation, Год журнала: 2023, Номер 134, С. 11 - 19

Опубликована: Сен. 13, 2023

Язык: Английский

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