Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis

Júnior, Constança; Ulldemolins, Anna; Narciso, Maria; Almendros, Isaac; Farré, Ramón; Navajas, Daniel; López, Javier; Eroles, Mar; Rico, Félix; Gavara, Núria

doi:10.3390/ijms24021708

Cited by 10 publications

(6 citation statements)

References 67 publications

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“…However, pulmonary fibrosis is a severe disease that affects the ECM in the lungs, stiffening over time, with patients having a short lifespan after diagnosis. Recent studies in the fibrotic rat lung have shown that the nanomechanical properties of the ECM change, inducing stiffening, and how the fibrotic architecture plays a role in it 38,244 …”

Section: Respiratory Diseasesmentioning

confidence: 99%

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Advances in mechanical biomarkers

Eroles

Rico

2023

J of Molecular Recognition

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Mechanical biomarkers distinguish health conditions through quantitative mechanical measurements. The emergence and establishment of nanotechnology in the last decades have provided new tools to obtain mechanical biomarkers at the nanoscale.Mechanical measurements are reproducible, label-free, start to be applied in vivo can be high throughput, and require small samples. Mechanical protocols in clinical practice at the macro scale like palpation or blood pressure measurement are routinely used by medical doctors. Nanotechnology brought mechanical sensing to the next scale, where cells, tissues, and proteins can be probed and linked to medical conditions. Mechanical changes in cells and tissues may be detected before other markers, such as protein expression, providing an important advantage as biomarkers. In the present review, we explore the biomarker's historical evolution, describe mechanical biomarkers on various diseases and novel discoveries in the nanomechanical field for their characterization. We conclude that mechanical biomarkers are establishing novel hallmarks in diseases, in several cases for early diagnostics of diseases and discovery of drug targets in the proteins involved in the mechanical changes, while advances in instrumentation are bringing commercial products into the clinical practice. Mechanical biomarkers along with clinical testing are establishing an important niche in the market, whose demand is increasing due to the expansion of personalized medicine and unmet needs in the clinics.

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Section: Respiratory Diseasesmentioning

confidence: 99%

“…Recent studies in the fibrotic rat lung have shown that the nanomechanical properties of the ECM change, inducing stiffening, and how the fibrotic architecture plays a role in it. 38,244…”

Section: Respiratory Diseasesmentioning

confidence: 99%

Advances in mechanical biomarkers

Eroles

Rico

2023

J of Molecular Recognition

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“…Studying the biomechanical behavior of bones helps to understand the mechanisms of fracture healing and how the healing process can be accelerated by surgical or other interventions. Lung diseases, especially dyspnea, often involve problems with respiratory airflow, lung tissue elasticity, and thoracic cavity mechanics (Júnior et al, 2023). Understanding these mechanical properties is important in the diagnosis and treatment of lung diseases.…”

Section: Afm Mechanics and Medical Challengesmentioning

confidence: 99%

Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics

Liu,

Han,

Kong

et al. 2023

Microscopy Res & Technique

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Despite significant progress in human medicine, certain diseases remain challenging to promptly diagnose and treat. Hence, the imperative lies in the development of more exhaustive criteria and tools. Tissue and cellular mechanics exhibit distinctive traits in both normal and pathological states, suggesting that “force” represents a promising and distinctive target for disease diagnosis and treatment. Atomic force microscopy (AFM) holds great promise as a prospective clinical medical device due to its capability to concurrently assess surface morphology and mechanical characteristics of biological specimens within a physiological setting. This review presents a comprehensive examination of the operational principles of AFM and diverse mechanical models, focusing on its applications in investigating tissue and cellular mechanics associated with prevalent diseases. The findings from these studies lay a solid groundwork for potential clinical implementations of AFM.Research HighlightsBy examining the surface morphology and assessing tissue and cellular mechanics of biological specimens in a physiological setting, AFM shows promise as a clinical device to diagnose and treat challenging diseases.

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“…Traditionally, when wound healing pathways are impaired, activated fibroblasts continue to recruit and accumulate, forming fibrotic areas in the lung. This faulty wound-healing process can cause ongoing remodeling of IPF and damage the extracellular matrix (ECM), leading to the progression of IPF and end-stage lung disease [ 17 ]. Cysteine cathepsins are usually found in lysosomes, where they are involved in intracellular protein turnover and are currently considered to be critical players in ECM remodeling in vivo [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Biomarker for the Progression of Idiopathic Pulmonary Fibrosis

Yeo,

Ha,

Shin

et al. 2024

IJMS

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The progression of idiopathic pulmonary fibrosis (IPF) is diverse and unpredictable. We identified and validated a new biomarker for IPF progression. To identify a candidate gene to predict progression, we assessed differentially expressed genes in patients with advanced IPF compared with early IPF and controls in three lung sample cohorts. Candidate gene expression was confirmed using immunohistochemistry and Western blotting of lung tissue samples from an independent IPF clinical cohort. Biomarker potential was assessed using an enzyme-linked immunosorbent assay of serum samples from the retrospective validation cohort. We verified that the final candidate gene reflected the progression of IPF in a prospective validation cohort. In the RNA-seq comparative analysis of lung tissues, CD276, COL7A1, CTSB, GLI2, PIK3R2, PRAF2, IGF2BP3, and NUPR1 were up-regulated, and ADAMTS8 was down-regulated in the samples of advanced IPF. Only CTSB showed significant differences in expression based on Western blotting (n = 12; p < 0.001) and immunohistochemistry between the three groups of the independent IPF cohort. In the retrospective validation cohort (n = 78), serum CTSB levels were higher in the progressive group (n = 25) than in the control (n = 29, mean 7.37 ng/mL vs. 2.70 ng/mL, p < 0.001) and nonprogressive groups (n = 24, mean 7.37 ng/mL vs. 2.56 ng/mL, p < 0.001). In the prospective validation cohort (n = 129), serum CTSB levels were higher in the progressive group than in the nonprogressive group (mean 8.30 ng/mL vs. 3.00 ng/mL, p < 0.001). After adjusting for baseline FVC, we found that CTSB was independently associated with IPF progression (adjusted OR = 2.61, p < 0.001). Serum CTSB levels significantly predicted IPF progression (AUC = 0.944, p < 0.001). Serum CTSB level significantly distinguished the progression of IPF from the non-progression of IPF or healthy control.

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Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis

Cited by 10 publications

References 67 publications

Advances in mechanical biomarkers

Advances in mechanical biomarkers

Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics

Development of a Novel Biomarker for the Progression of Idiopathic Pulmonary Fibrosis

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