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, e...
April 23, 2020
Journal:
Int J Rheum Dis
Author:
Kubo S, Siebuhr AS, Bay-Jensen AC, Juhl P, Karsdal MA, Satoh Y, Todoroki Y, Nakano K, Nakayamada S, Tanaka Y
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, remodelling infers a dynamic process that would require a spatiotemporal resolution. This review focuses on differ...
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 that...
December 2, 2019
Journal:
Lancet Respir Med
Author:
Manon-Jensen T, Langholm LL, Ronnow SR, Karsdal MA, Tal-Singer R, Vestbo J, Leeming DJ, Miller BE, bülow Sand JM
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th...
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 ty...
October 1, 2018
Journal:
chest
Author:
Schuppan D, Leeming DJ, papakonstantinou E, Kostikas K, Boersma W, Louis R, Milenkovik B, Aerts J, Sand JM, Wouters EFM, Rohde G, Prat C, Torres A, Welte T, Tamm M, Karsdal M, Stolz D
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...
September 10, 2018
Journal:
Biochem Biophys Res Commun
Author:
Gudmann NS, Manon-Jensen T, Sand JMB, Diefenbach C, Sun S, Danielsen A, Karsdal MA, Leeming DJ
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...
August 1, 2018
Journal:
Cancer biology therapy
Author:
Kehlet SN, Manon-Jensen T, Sun S, Brix S, Karsdal MA, Leeming DJ, Willumsen N
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 exac...
May 4, 2018
Journal:
Respir Res
Author:
Sand JMB, Tanino Y, Karsdal MA, Nikaido T, Misa K, Sato Y, Togawa R, Wang X, Leeming DJ, Munakata M
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 observational,...
December 4, 2017
Journal:
BMC Pulm Med.
Author:
Leeming DJ, Byrjalsen I, Sand JMB, Bihlet AR, Lange P, Thal-Singer R, Miller BE, Karsdal MA, Vestbo J
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 mortalit...
October 4, 2016
Journal:
Respir Res.
Author:
Sand JM, Leeming DJ, Byrjalsen I, Bihlet AR, Lange P, Tal-Singer R, Miller BE, Karsdal MA, Vestbo J
OBJECTIVES: hronic 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 a...
September 7, 2016
Journal:
Clin Biochem
Author:
Lange P, Leeming DJ, Karsdal MA, Midjord AK, Martinez G, Sand JM
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 aberrant ...
August 1, 2016
Journal:
Thorax
Author:
Mercer PF, Woodcock HV, Eley JD, Platé M, Sulikowski MG, Durrenberger PF, Franklin L, Nanthakumar CB, Man Y2, Genovese F, McAnulty RJ, Yang S, Maher TM, Nicholson AG, Arbit E, Marshall RP, Lukey PT, Chambers RC
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 aberrant ...
August 1, 2016
Journal:
Thorax
Author:
Mercer PF, Woodcock HV, Eley JD, Platé M, Sulikowski MG, Durrenberger PF, Franklin L, Nanthakumar CB, Man Y2, Genovese F, McAnulty RJ, Yang S, Maher TM, Nicholson AG, Arbit E, Marshall RP, Lukey PT, Chambers RC
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 of...
July 5, 2016
Journal:
Respir Res.
Author:
Hansen NU, Karsdal MA, Brockbank S, Cruwys S, Rønnow S, Christiansen C
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 ...
July 9, 2015
Journal:
Clin Biochem
Author:
Kristensen JH, Larsen L, Dasgupta B, Brodmerkel C, Curran M, Karsdal MA, Sand JM, Willumsen N, Knox AJ, Bolton CE, Johnson SR, Hägglund P, Svensson B, Leeming DJ
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...
July 1, 2015
Journal:
Chest
Author:
Bihlet AR, Karsdal MA, Bay-Jensen AC, Read S, Kristensen JH, Sand JM, Leeming DJ, Andersen JR, Lange P, Vestbo J
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 progressi...
June 11, 2015
Journal:
Respir Res.
Author:
Sand JM, Knox AJ, Lange P, Sun S, Kristensen JH, Leeming DJ, Karsdal MA, Bolton CE, Johnson SR
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 ant...
May 3, 2015
Journal:
BMC Pulm Med.
Author:
Kristensen JH, Karsdal MA, Sand JM, Willumsen N, Diefenbach C, Svensson B, Hägglund P, Oersnes-Leeming DJ
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...
October 29, 2014
Journal:
Respiration
Author:
Kristensen JH, Karsdal MA, Genovese F, Johnson S, Svensson B, Jacobsen S, Hägglund P, Leeming DJ
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 rel...
December 13, 2013
Journal:
PLoS One
Author:
Sand JM, Larsen L, Hogaboam CM, Martinez F, Han M, Røssel Larsen M, Nawrocki A, Zheng Q, Karsdal MA, Leeming DJ
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,...
November 8, 1983
Journal:
Int J Chron Obstruct Pulmon
Author:
Langholm LL, Rønnow S, bülow Sand JM, Leeming DJ, Talsinger R, Miller BE, Vestbo J, Karsdal MA, Manon-Jensen T
Introduction: 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...
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