Abstract

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 the diagnostic features of neo-epitope fragments of type III collagen generated by cathepsins that could reflect the pathological tissue turnover in patients with different diseases. A novel enzyme-linked immunosorbent assay (ELISA) measuring cathepsins B, L, S and K -generated type III collagen fragments (C3C) was developed for assessment in serum and plasma. The assay was biologically validated in serum from patients with chronic obstructive pulmonary disease (COPD). Serological levels of C3C were significantly elevated in patients with COPD compared to healthy controls (p = 0.0006). Levels of C3C in serum and heparin plasma of COPD patients had a highly significant correlation (R2 = 0.86, p<0.0001). The data suggests that the C3C fragment is elevated in patients with COPD compared to healthy controls.

Highlights

  • Fibrillar collagens, such as type I and III collagen, are some of the most prominent collagens in the extracellular matrix (ECM) of the lung [1,2,3]

  • We developed and characterized the novel competitive enzyme-linked immunosorbent assay (ELISA) C3C using a monoclonal antibody detecting neo-epitope fragments of type III collagen generated by the proteases cathepsins

  • Our data suggest that there is an elevated level of cathepsin B, L, S or K activity and/or an upregulated type III collagen production in patients with chronic obstructive pulmonary disease (COPD) giving rise to a higher level of type III collagen fragments containing the C3C neo-epitope

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Summary

Introduction

Fibrillar collagens, such as type I and III collagen, are some of the most prominent collagens in the extracellular matrix (ECM) of the lung [1,2,3]. Fibrillar collagens provide tensile strength which enables enlargement of the lung components such as the alveoli, vessels, and connective tissue sheaths. An important requirement for balanced remodeling of the ECM is a tight control of enzymes involved in its turnover. A Novel ELISA Targeting a Neo-Epitope of Cathepsin-Mediated Turnover of Type III Collagen. DGKR, JMBS, MAK, and FGE, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ’author contributions’ section

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