33 Publication(s) found
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Rheumatology, Systemic Sclerosis, Respiratory System, Extracellular Matrix Research
23. Apr 2020

Correlation Between Serological Biomarkers of Extracellular Matrix Turnover and Lung Fibrosis and Pulmonary Artery Hypertension in Patients With Systemic Sclerosis

Objective: To determine the value of serological biomarkers of collagen degradation/turnover as serum markers of organ involvement in patients with systemic sclerosis (SSc).

Methods: Serum samples were obtained from 79 SSc patients and 19 healthy control subjects. Types I to VI collagen turnover,…

Respiratory System, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research
9. Mar 2020

Increased Von Willebrand Factor Processing in COPD, Reflecting Lung Epithelium Damage, Is Associated With Emphysema, Exacerbations and Elevated Mortality Risk

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and lung tissue deterioration. Given the high vascularity of the lung, von Willebrand factor (VWF), a central component of wound healing initiation, has previously been assessed in COPD. VWF processing,…

Respiratory System, Extracellular Matrix Research, Biomarker position
26. Jan 2020

Lost in transition: biomarkers of remodeling in patients with asthma.

PURPOSE OF REVIEW:
'Biomarkers of remodeling' represent a loose collection of features referring to several biological adaptations of the lung to cope with stressing factors. In addition, remodel-'ing' infers a dynamic process that would require a spatiotemporal resolution. This review focuses on d…

Respiratory System, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research
2. Dec 2019

End-product of fibrinogen is elevated in emphysematous chronic obstructive pulmonary disease and is predictive of mortality in the ECLIPSE cohort.

BACKGROUND:
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair process that may result in intra-airway accumulation of fibrin. Given that plasma fibrinogen is the only FDA approved biomarker that predicts mortality and COPD exacerbations, we hypothesized tha…

Respiratory System, Lung, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research, Biomarker position
26. Nov 2019

Post-translational modifications of vimentin reflect different pathological processes associated with non-small cell lung cancer and chronic obstructive pulmonary disease.

Vimentin has shown to be highly implicated in cancer initiation and progression. Vimentin is often a target of post-translational modifications (PTMs) which can be disease specific, thus targeting these specific modifications can be of high biomarker potential. In this study we set out to evaluate t…

Respiratory System, Biomarker position, Extracellular Matrix Research, Idiopathic Pulmonary Fibrosis
12. Jul 2019

Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort.

Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was ass…

Cardiovascular System, Respiratory System
17. May 2019

Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone

Cardiac fibrosis contributes to the development of heart failure in pulmonary hypertension. We aimed to assess the development of fibrosis and the effects of treatment with the anti-fibrotic agent pirfenidone in pressure overload induced right ventricular (RV) failure. Wistar rat weanlings were rand…

Respiratory System, Chronic Obstructive Pulmonary Disease
9. Mar 2019

Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort

Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es…

Extracellular Matrix Research, Respiratory System, Idiopathic Pulmonary Fibrosis, Lung, Chronic Obstructive Pulmonary Disease
12. Feb 2019

Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders

OBJECTIVES:
Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which …

Idiopathic Pulmonary Fibrosis, Respiratory System, Oncology, Lung, Extracellular Matrix Research
2. Jan 2019

The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis.

Myofibroblasts are the key effector cells responsible for excessive extracellular matrix deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). The PI3K/Akt/mTOR axis has been implicated in fibrosis, with pan-PI3K/mTOR inhibition currently under clinical evaluatio…

Respiratory System, Idiopathic Pulmonary Fibrosis, Oncology, Lung
30. Nov 2018

A serological marker of the N-terminal neoepitope generated during LOXL2 maturation is elevated in patients with cancer or idiopathic pulmonary fibrosis

OBJECTIVES:
Lysyl oxidase like 2 (LOXL2) is associated with poor prognosis in idiopathic pulmonary disease (IPF) and cancer. We developed an Enzyme-linked immunosorbent assay (ELISA) targeting the LOXL2 neo-epitope generated through the release of the signal peptide during LOXL2 maturation.

DESI…

Respiratory System, Chronic Obstructive Pulmonary Disease
1. Oct 2018

Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease.

BACKGROUND:
The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of t…

Chronic Obstructive Pulmonary Disease, Respiratory System
10. Sep 2018

Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio…

Respiratory System, Chronic Obstructive Pulmonary Disease
10. Sep 2018

Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio…

Lung, Respiratory System, Oncology
1. Aug 2018

A fragment of SPARC reflecting increased collagen affinity shows pathological relevance in lung cancer - implications of a new collagen chaperone function of SPARC

The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) is known to bind collagens and regulate fibrillogenesis. Cleavage of SPARC at a single peptide bond, increases the affinity for collagens up to 20-fold. To investigate if this specific cleavage has pathological relevance…

Respiratory System, Extracellular Matrix Research
4. May 2018

A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia

BACKGROUND:
Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exa…

Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis, Lung, Extracellular Matrix Research
7. Mar 2018

Tumstatin, a Matrikine Derived from Collagen Type IVα3, is Elevated in Serum from Patients with Non-Small Cell Lung Cancer

OBJECTIVES
Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tums…

Extracellular Matrix Research, Systemic Sclerosis, Rheumatology, Chronic Obstructive Pulmonary Disease
1. Mar 2018

Development of a Neo-Epitope Specific Assay for Serological Assessment of Type VII Collagen Turnover and Its Relevance in Fibroproliferative Disorders

Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients wi…

Chronic Obstructive Pulmonary Disease, Respiratory System
4. Dec 2017

Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study

BACKGROUND:
Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1.

METHODS:
One thousand COPD subjects from the observatio…

Chronic Obstructive Pulmonary Disease
11. Jan 2017

Development of a Novel Enzyme-Linked Immunosorbent Assay Targeting a Neo-Epitope Generated by Cathepsin-Mediated Turnover of Type III Collagen and Its Application in Chronic Obstructive Pulmonary Disease

A high level of extracellular matrix (ECM) turnover characterizes several lung diseases with fibrotic features. Type III collagen is one of the most abundant collagens in lung parenchyma, and cathepsins play a role in lung pathology, being responsible for tissue remodeling. In this study, we explore…

Extracellular Matrix Research, Respiratory System
4. Oct 2016

High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD - results from the ECLIPSE study

BACKGROUND:
There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortali…

Respiratory System, Chronic Obstructive Pulmonary Disease
7. Sep 2016

Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease

OBJECTIVES:
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been…

Chronic Obstructive Pulmonary Disease
26. Aug 2016

Systemic Biomarkers of Collagen and Elastin Turnover Are Associated With Clinically Relevant Outcomes in COPD

BACKGROUND:
Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD.

METHODS…

Respiratory System
1. Aug 2016

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

RATIONALE:
Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberran…

Extracellular Matrix Research, Respiratory System
5. Jul 2016

Tissue turnover of collagen type I, III and elastin is elevated in the PCLS model of IPF and can be restored back to vehicle levels using a phosphodiesterase inhibitor

BACKGROUND:
The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination …

Respiratory System, Idiopathic Pulmonary Fibrosis
9. Jul 2015

Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders

OBJECTIVES:
Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the…

Respiratory System, Chronic Obstructive Pulmonary Disease
1. Jul 2015

Clinical Drug Development Using Dynamic Biomarkers to Enable Personalized Health Care in COPD

Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical development o…

Chronic Obstructive Pulmonary Disease, Respiratory System
11. Jun 2015

Accelerated extracellular matrix turnover during exacerbations of COPD

BACKGROUND:
Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progress…

Respiratory System, Chronic Obstructive Pulmonary Disease
3. May 2015

Serological assessment of neutrophil elastase activity on elastin during lung ECM remodeling

BACKGROUND:
During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for an…

Respiratory System, Extracellular Matrix Research
29. Oct 2014

The role of extracellular matrix quality in pulmonary fibrosis

This review discusses the role of extracellular matrix (ECM) quality in the pathogenesis of pulmonary fibrosis (PF). In PF, the highly ordered structure of collagens and elastin within the ECM of the lung is severely disrupted and lacks its original tissue quality. Discussions about the ECM have foc…

Respiratory System, Chronic Obstructive Pulmonary Disease
13. Dec 2013

MMP mediated degradation of type IV collagen alpha 1 and alpha 3 chains reflects basement membrane remodeling in experimental and clinical fibrosis--validation of two novel biomarker assays

OBJECTIVES:
Fibrosis is characterized by excessive tissue remodeling resulting from altered expression of various growth factors, cytokines and proteases. We hypothesized that matrix metalloproteinase (MMP) mediated degradation of type IV collagen, a main component of the basement membrane, will re…

Respiratory System, Idiopathic Pulmonary Fibrosis, Chronic Obstructive Pulmonary Disease
20. Jul 2012

Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

BACKGROUND:
Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in …

Respiratory System, Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis
11. Jul 2012

Serological investigation of the collagen degradation profile of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis

In both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), abnormally high collagen remodeling occurs within the lung tissue. Matrix metalloproteinase (MMP)-degraded type I, III, IV, V and VI collagen and a disintegrin and metalloproteinase with thrombospondin moti…