34 Publication(s) found
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Type 2-Diabetes, Endocrinology, Extracellular Matrix Research
11. Apr 2018

Higher collagen VI formation is associated with all-cause mortality in type 2 diabetic patients with microalbuminuria

OBJECTIVE:
Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI fo…

Extracellular Matrix Research, Atherosclerosis
31. Mar 2018

Assessment of extracellular matrix-related biomarkers in patients with lower extremity artery disease

BACKGROUND:
The prevalence of lower extremity artery disease (LEAD) is high (20%-25%) in the population older than 65 years, but patients are seldom identified until the disease is advanced. Circulating markers of disease activity might provide patients with a key opportunity for timely treatment. …

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…

Cardiovascular System, Extracellular Matrix Research, Myocardial Fibrosis
1. Jan 2018

Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy

AIM:
Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patie…

Cardiovascular System, Extracellular Matrix Research
14. Dec 2017

Understanding Cardiac Extracellular Matrix Remodeling to Develop Biomarkers of Myocardial Infarction Outcomes

Cardiovascular Disease (CVD) is the most common cause of death in industrialized countries, and myocardial infarction (MI) is a major CVD with significant morbidity and mortality. Following MI, the left ventricle (LV) undergoes a wound healing response to ischemia that results in extracellular matri…

Renal System, Chronic Renal Disease
11. Dec 2017

Urinary endotrophin predicts disease progression in patients with chronic kidney disease

Renal fibrosis is the central pathogenic process in progression of chronic kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal fibrosis. Endotrophin is released from COL VI and promotes pleiotropic pro-fibrotic effects. Kidney disease severity varies considerably and accurate inf…

Extracellular Matrix Research, Peripheral Vascular Disease
12. Aug 2017

Non-invasive evaluation of extracellular matrix remodeling in peripheral artery disease

AIM:
Peripheral artery disease (PAD) is a common manifestation of systemic atherosclerosis affecting peripheral arteries. The underlying pathology of PAD are disorganized extracellular matrix (ECM), caused by inflammation and oxidation. Previous studies have demonstrated an important structure dis…

Renal System, Type 2-Diabetes, Obesity
26. Jul 2017

High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy

ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates …

Renal System, Chronic Renal Disease
21. Apr 2017

Non-invasive quantification of collagen turnover in renal transplant recipients

Kidney allograft failure due to chronic injury/rejection remains the main cause of graft loss in renal transplant recipients (RTR). Here, we investigated whether specific biomarkers of extracellular matrix (ECM) turnover are associated with allograft function and chronic kidney disease (CKD) stage i…

Chronic Renal Disease, Renal System
12. Apr 2017

Serum endotrophin, a type VI collagen cleavage product, is associated with increased mortality in chronic kidney disease

BACKGROUND:
Patients with chronic kidney disease (CKD) are at increased risk of end-stage renal disease (ESRD) and early mortality. The underlying pathophysiological processes are not entirely understood but may include dysregulation of extracellular matrix formation with accelerated systemic and r…

Chronic Renal Disease
20. Mar 2017

Urinary collagen degradation products as early markers of progressive renal fibrosis

BACKGROUND:
Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic…

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…

Type 2-Diabetes
8. Sep 2016

Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes

AIMS/HYPOTHESIS:
The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of pro…

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, Renal System
22. May 2016

Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis

The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) su…

Renal System
1. Feb 2016

Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease

During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for catheps…

Extracellular Matrix Research
21. Dec 2015

Protein degradation fragments as diagnostic and prognostic biomarkers of connective tissue diseases: understanding the extracellular matrix message and implication for current and future serological biomarkers

The aim of this review is to discuss the potential usefulness of novel biochemical markers of connective tissues: neo-epitopes of extracellular matrix proteins generated by post-translational modifications by tissue proteinases. As each modification results from a specific local physiological or pat…

Extracellular Matrix Research
22. Aug 2015

Collagen and tissue turnover as function of age - implications for fibrosis

BACKGROUND:
The extracellular matrix (ECM) is the backbone of all tissues. It is a complex grid consisting of multiple structural proteins which each play a vital role for the function and maintenance of normal tissue function. In development and growth, tissue is being formed and elaborated (tissu…

Renal System, Chronic Renal Disease
1. Jul 2015

Serum and urine markers of collagen degradation reflect renal fibrosis in experimental kidney diseases

BACKGROUND:
The extent of renal fibrosis in chronic kidney disease (CKD) is the best predictor for progression of most renal diseases. To date, no established biomarkers of renal fibrosis exist.

METHODS:
We measured circulating and urinary-specific matrix metalloproteinase (MMP)-generated colla…

Hepatic System, Non-Alcoholic Fatty Liver Disease
15. May 2015

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential…

Extracellular Matrix Research, Renal System, Chronic Renal Disease
26. Apr 2015

Turnover of type III collagen reflects disease severity and is associated with progression and microinflammation in patients with IgA nephropathy

BACKGROUND:
Renal fibrosis is the hallmark of progression to end-stage kidney disease. Non-invasive biomarkers of renal fibrosis could serve as specific end points in clinical trials and improve monitoring and stratification of patients with chronic kidney disease (CKD). To address this, we measure…

Extracellular Matrix Research
1. Apr 2015

The importance of extracellular matrix for cell function and in vivo likeness

OBJECTIVE:
Fibrotic diseases may be described as a disease of the extracellular matrix, where the balance between matrix formation and degradation has been shifted leading to an accumulation of matrix. Currently a fit for purpose model and readily available approach are adapted when doing cell cult…

Rheumatology, Alkaptonuria
1. Mar 2015

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-…

Rheumatology, Gout
1. Jan 2015

Investigating the Robustness and Diagnostic Potential of Extracellular Matrix Remodelling Biomarkers in Alkaptonuria

BACKGROUND AND AIM:
Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKU patients. We tested a panel of serum and urinary biomarkers reflecting extracellular matr…

Rheumatology, Osteoarthritis
4. Dec 2014

Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment

BACKGROUND:
Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied.

METHOD…

Renal System, Extracellular Matrix Research
29. Oct 2014

Association of versican turnover with all-cause mortality in patients on haemodialysis

OBJECTIVE:
Cardiovascular diseases are among the most common causes of mortality in renal failure patients undergoing haemodialysis. A high turnover rate of the proteoglycan versican, represented by the increased presence of its fragmentation products in plasma, has previously been associated with …

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…

Renal System, Extracellular Matrix Research
28. Mar 2014

The extracellular matrix in the kidney: a source of novel non-invasive biomarkers of kidney fibrosis?

Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease (CKD) leading to kidney failure. The clinical course of many renal diseases, and thereby of CKD, is highly variable. One of the major challenges in deciding which treatment approach is best suited for a patient but also…

Extracellular Matrix Research, Cardiovascular System, Atherosclerosis
3. Jun 2013

A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease

Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current …

Extracellular Matrix Research, Hepatic System
15. May 2013

Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases

BACKGROUND:
The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and li…

Extracellular Matrix Research
11. Mar 2013

Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure

Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive ti…

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…

Extracellular Matrix Research, Cardiovascular System, Acute Myocardial Infarct
6. Jul 2012

Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker

BACKGROUND:
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical s…

Hepatic System, Extracellular Matrix Research
3. Jan 2012

Molecular serum markers of liver fibrosis

Fibrosis is a hallmark histologic event of chronic liver diseases and is characterized by the excessive accumulation and reorganization of the extracellular matrix (ECM). The gold standard for assessment of fibrosis is liver biopsy. As this procedure has various limitations, including risk of patien…