Circulating endotrophin is an early marker of kidney disease development in persons with type 2 diabetes
Introduction
NordicEndotrophin™ (Endotrophin), a pro-fibrotic fragment generated during collagen type VI formation, measured by nordicPRO-C6™, has been largely investigated as a biomarker of adverse outcome in persons with diabetic kidney disease. We investigated its potential to predict kidney disease onset in two independent type 2 diabetes (T2D) cohorts.
Circulating nordicEndotrophin™, measured by the nordicPRO-C6™ assay, was a risk marker for kidney outcomes in people with T2D without or with early kidney disease. This adds to the evidence that nordicEndotrophin™is a relevant biomarker of kidney complications in T2D, even in persons with no or mild kidney disease at baseline.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Development of a novel assay to quantify circulating full-length endotrophin and validation as a risk marker of complications in T2D
Introduction
NordicEndotrophin™ (ETP), a bioactive fragment of type VI collagen (COL6), has been widely evaluated as a biomarker of risk of outcome in type 2 diabetes (T2D). The most used assay to quantify ETP is a competitive ELISA employing an antibody targeting the C-terminal of the α3 chain of COL6, encompassing part of the ETP sequence (nordicPRO-C6™).
We developed a sandwich ELISA targeting full-lenght ETP (nordicEndotrophin™), which employes an antibody targeting the N-terminal end of the ETP molecule and the antibody targeting the C-terminal end of COL6A3 (nordicPRO-C6™). We evaluated the potential of the two assays as risk markers of T2D adverse outcomes.
The nordicEndotrophin™ assay is a technically robust sandwich ELISA quantifying the full-lenght endotrophin molecule in circulation. This biomarker presents a similar, or possibly higher prognostic power for complications of T2D than the competitive ELISA nordicPRO-C6™, used so far to quantify nordicEndotrophin™ in circulation.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Activated macrophage-conditioned media induces fibrogenesis in a gastrointestinal scar-in-a-jar model that is quantifiable with serological biomarkers of collagen formation
Introduction
Intestinal fibrosis affects most inflammatory bowel disease (IBD) patients, resulting in severe clinical complications and reduced treatment response. Driven primarily by myofibroblasts, this condition is characterized by the excessive accumulation of extracellular matrix in the intestines. With no treatments approved for intestinal fibrosis, there is a need for preclinical models to investigate the pathobiology and novel treatments.
In this study we investigated the profibrotic effects of activated macrophages (Mφ) in a scar-in-a-jar model of colonic fibrogenesis using validated protein fingerprint assay (PFA) biomarkers of collagen formation.
The noninvasive PFA biomarkers can be used to objectively quantify fibrogenesis in the in vitro Scar-in-a-Jar model, providing a valuable tool for investigating the underlying mechanisms of fibrogenesis.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Degradation of the alveolar basement membrane type IV collagen alpha-3 chain is associated with antifibrotic treatment and pulmonary hypertension in idiopathic pulmonary fibrosis
Introduction
Idiopathic pulmonary fibrosis (IPF) is a rare but devastating disease with inevitable progression and high mortality. Currently, Pirfenidone and Nintedanib are the only approved antifibrotic treatment options to slow disease progression. Additionally, a pulmonary hypertension (PH) complication can further worsen disease outcome and quality of life. Forced vital capacity (FVC) is currently the most employed endpoint in clinical trials to monitor disease progression for antifibrotic treatment (Tx) development.
Molecularly, the extracellular matrix is subjected to excessive, pathological remodeling during IPF progression. Type IV collagen (COL4) is a critical part of the basement membrane that support the epithelium and crucial to cellular integrity. Mature COL4 are trimers that can be derived from six different alpha-chains, wherein the a3-chain is predominantly expressed in alveoli. Other trimers are expressed ubiquitously.
The aim was to investigate potential associations with antifibrotic Tx and PH in IPF patients by comparing serological levels of alveolar basement membrane degradation by a fragment of the COL4 alpha-3 chain (C4Ma3) with a fragment of more general remodeling by the alpha-1 chain (PRO-C4).
The COL4 alpha-3 chain has limited tissue distribution and is crucial for alveolar function. In this study, higher levels of COL4 alpha-3 chain degradation (C4Ma3) was:
found in IPF with PH.
associated with no antifibrotic treatment, indicating a pharmacodynamic potential.
In comparison, the COL4 alpha-1 chain marker PRO-C4, indicating ubiquitous basement membrane remodeling, did not show statistically different levels between any of the groups compared in this study. This could highlight the fact that damage done within alveoli are especially relevant when assessing the effect of antifibrotic Tx and PH in IPF.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Reduction of PRO-C3 and PRO-C6 fibrogenesis biomarkers inconnective tissue disease-associated interstitial lung disease:results from the Phase IIb RECITAL trial
Introduction
Interstitial lung disease (ILD) is a major cause of morbidity and mortality in connective tissue disease (CTD). While cyclophosphamide is often an effective treatment for CTD-ILD, its use is limited by side effects.
In this study, Rituximab was tested as an alternative in the RECITAL phase IIb trial(NTC1862926). Both drugs improved 24- and 48-week lung function with rituximab showing fewer adverse events.
The decrease in nordicPRO-C6™ and nordicPRO-C3™ suggest that, besides their immunomodulatory effects, these drugs may also reduce fibrogenesis. NordicPRO-C3™ and nordicPRO-C6™, measured at baseline and as % change from baseline, are associated with an FVC response. These findings highlight nordicPRO-C3™ and nordicPRO-C6™ as promising biomarkers for CTD-ILD.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
