21 Publication(s) found
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Respiratory System, Chronic Obstructive Pulmonary Disease
1. Oct 2018

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

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…

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

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

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

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.

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

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

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

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.


Respiratory System
1. Aug 2016

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

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

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

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

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

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

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

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…