The engineering and application of extracellular matrix hydrogels: a review

Biomaterials Science, Год журнала: 2023, Номер 11(11), С. 3784 - 3799

Опубликована: Янв. 1, 2023

The engineering and appliccations of ECM hydrogels.

Язык: Английский

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Identification of tyrosine brominated extracellular matrix proteins in normal and fibrotic lung tissues

Redox Biology, Год журнала: 2024, Номер 71, С. 103102 - 103102

Опубликована: Фев. 23, 2024

Peroxidasin (PXDN) is a secreted heme peroxidase that catalyzes the oxidative crosslinking of collagen IV within extracellular matrix (ECM) via intermediate hypobromous acid (HOBr) synthesis from hydrogen peroxide and bromide, but recent findings have also suggested alternative ECM protein modifications by PXDN, including incorporation bromide into tyrosine residues. In this work, we sought to identify major target proteins for bromination HOBr or PXDN-mediated oxidation in mouse teratocarcinoma PFHR9 cells. We detected 61 bromotyrosine (BrY)-containing peptides representing 23 HOBr-modified cells, among which laminins displayed most prominent incorporation. Moreover, found laminin α1, β1, tubulointerstitial nephritis antigen-like (TINAGL1) contained BrY untreated depended on PXDN. extended these analyses lung tissues both healthy mice with experimental fibrosis, obtained human subjects. Analysis ECM-enriched tissue extracts showed 83 were elevated bleomycin-induced included various collagens laminins, Similarly, mRNA expression PXDN α/β1 enhanced fibrotic tissues, bone-marrow-derived macrophages fibroblasts stimulated transforming growth factor profibrotic factor. identified 11 BrY-containing proteins, α2, VI TINAGL1, although relative extent was not significantly increased during fibrosis. Finally, 7 again TINAGL1. Altogether, work demonstrates presence several bromotyrosine-modified likely involving even normal suggesting potential biological function modifications.

Язык: Английский

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Pharmacological targeting of ECM homeostasis, fibroblast activation, and invasion for the treatment of pulmonary fibrosis

Expert Opinion on Therapeutic Targets, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with dismal prognosis. While the standard-of-care (SOC) drugs approved for IPF represent significant advancement in antifibrotic therapies, they primarily slow progression and have limited overall efficacy many side effects. Consequently, remains condition high unmet medical pharmacological needs.

Язык: Английский

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Study on the changes of extracellular matrix morphology and components in COPD animal model by using lung decellularized scaffold

The FASEB Journal, Год журнала: 2025, Номер 39(6)

Опубликована: Март 27, 2025

Abstract Airway remodeling is a critical pathological process that influences the progression of chronic obstructive pulmonary disease(COPD). To better study small airway in COPD, we employed advanced techniques such as decellularized scaffolds, immunofluorescence, scanning electron microscopy, and proteomics to analyze morphological compositional changes extracellular matrix (ECM). Our revealed significant ultrastructural abnormalities scaffolds from COPD group, including thinning alveolar septa, enlargement spaces, fusion multiple alveoli. Additionally, ECM composition group exhibited notable characterized by an increase collagen fibers, type I IV collagens, fibronectin, laminin ( p < .05), along with decrease elastin glycosaminoglycans .05). Proteomic analysis identified 70 differentially expressed proteins between control group. These included 34 upregulated Smarca2, Skt, Acvrl1, Myl2 (all ratios >10.64), 36 downregulated Col6a6, Col6a5, AnK3 <0.27). Pathway indicated activation apoptosis (Enrichment Score, ES = 0.23) epithelial–mesenchymal transition (ES 0.38) genes inhibition synthesis –0.43) degradation –0.63) were observed findings enhance our understanding mechanisms underlying provide scientific basis for developing novel therapeutic strategies COPD.

Язык: Английский

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Extracellular Matrix as a Driver of Chronic Lung Diseases

American Journal of Respiratory Cell and Molecular Biology, Год журнала: 2024, Номер 70(4), С. 239 - 246

Опубликована: Янв. 8, 2024

The extracellular matrix (ECM) is not just a three-dimensional scaffold that provides stable support for all cells in the lungs, but also an important component of chronic fibrotic airway, vascular, and interstitial diseases. It bioactive entity dynamically modulated during tissue homeostasis disease, controls structural immune cell functions drug responses, can release fragments have biological activity be used to monitor disease activity. There growing recognition importance considering ECM changes diseases, including

Язык: Английский

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Collagen-targeted PET imaging for progressive experimental lung fibrosis quantification and monitoring of efficacy of anti-fibrotic therapies

Theranostics, Год журнала: 2025, Номер 15(6), С. 2092 - 2103

Опубликована: Янв. 13, 2025

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by an excessive collagen deposition ultimately leading to tissue stiffening and functional decline. Beyond IPF, other are often associated with connective diseases may develop in ∼18-32% of patients. Therapeutic options limited nintedanib pirfenidone which only able reduce progression without curing it. The current lack biomarker accurately assess predict therapy efficacy for IPF remains major clinical concern. Methods: In our study, was monitored bleomycin-induced lung mice vivo molecular imaging using collagen-targeted radiopharmaceutical, [68Ga]Ga-NODAGA-collagelin. Fibrosis also computed tomography, the gold standard technique detect Results: We demonstrated that increase content can be quantified [68Ga]Ga-NODAGA-collagelin PET correlation stage severity. uptake mainly found fibrotic areas lungs bleomycin-receiving mice. Most interestingly, allowed non-invasive monitoring as well anti-fibrotic effect JAK inhibitor, tofacitinib. Conclusion: Thus, appears promising tool staging, prediction towards personalized medicine IPF.

Язык: Английский

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Effects of aging on the biomechanical properties of the lung extracellular matrix: dependence on tissular stretch

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Апрель 5, 2024

Introduction: Aging induces functional and structural changes in the lung, characterized by a decline elasticity diminished pulmonary remodeling regenerative capacity. Emerging evidence suggests that most biomechanical alterations lung result from composition of extracellular matrix (ECM), potentially modulating behavior cells increasing susceptibility to chronic diseases. Therefore, it is crucial investigate mechanical properties aged lung. This study aims assess ECM due aging at both residual (RV) (FV) volumes evaluate their effects on survival proliferation mesenchymal stromal (MSCs). Methods: The lungs young (4-6-month-old) (20-24-month-old) mice were inflated with optimal cutting temperature compound reach FV or non-inflated (RV). proteins laminin, collagen I fibronectin quantified immunofluorescence decellularized sections assessed using atomic force microscopy. To whether and/or RV affects MSCs, viability evaluated after 72 h. Results: Laminin presence was significantly reduced compared mice, while increased mice. In conditions, acellular softer than By contrast, becomes stiffer revealing strain hardening depends aging. Results MSCs recellularization showed similar rate all conditions. Discussion: data strongly measurements, especially models, should be carried out physiomimetic conditions rather following conventional approach. use scaffolds other disease murine/human models will help better understand potential role mechanotransduction progression diseases, regeneration cancer.

Язык: Английский

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The tumor microbiome composition of non-small cell lung carcinoma correlates with expression differences in genes related with immunity, proteolysis and the extracellular matrix remodeling

Next research., Год журнала: 2025, Номер unknown, С. 100116 - 100116

Опубликована: Янв. 1, 2025

Язык: Английский

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Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis

Proteomes, Год журнала: 2025, Номер 13(1), С. 3 - 3

Опубликована: Янв. 13, 2025

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by repetitive alveolar injuries with excessive deposition of extracellular matrix (ECM) proteins. A crucial need in understanding IPF pathogenesis identifying cell types associated histopathological regions, particularly local centers known as fibroblast foci. To address this, we integrated published spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) adopted the Query method Overlap to determine type enrichments regions. Distinct are highly foci, transitional 2 aberrant KRT5-/KRT17+ (KRT: keratin) epithelial cells morphologically normal alveoli human lungs. Furthermore, employed laser capture microdissection-directed mass spectrometry profile By comparing another similar dataset, common differentially expressed proteins enriched pathways related ECM structure organization collagen processing were identified Importantly, enrichment results from innovative proteomics scRNA-seq data integration accord those integration, supporting capability versatility entire approach. In summary, multi-omics identify disease-associated potential targets for novel therapies intervention. The approach can be further applied other areas heterogeneity.

Язык: Английский

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Influence of Lung Extracellular Matrix from non-IPF and IPF Donors on Primary Human Lung Fibroblast Biology

Biomaterials Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Fibrosis, a hallmark of chronic lung disease, involves ECM remodeling. This work shows that decellularized from IPF lungs—with its unique biochemical composition—can promote profibrotic fibroblast phenotype.

Язык: Английский

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