TY - JOUR

T1 - The role of extracellular matrix quality in pulmonary fibrosis

AU - Kristensen, Jacob Hull

AU - Karsdal, Morten Asser

AU - Genovese, Federica

AU - Johnson, Simon

AU - Svensson, Birte

AU - Jacobsen, Susanne

AU - Hägglund, Per

AU - Leeming, Diana Julie

PY - 2014

Y1 - 2014

N2 - 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 focused on the role of protein quantity in relation to the progression of PF, while the importance of lung ECM quality, defined by the levels of ECM protein modifications and by the protein distribution in lung tissue, has not been properly addressed. The quality and function of proteins may be altered by different post-translational modifications (PTMs), such as cross-linking, proteolytic cleavage, citrullination, misfolding and glycosylation. This paper is the first to review key data from the literature related to the lung ECM at the molecular level, relate these to changes observed at a macroscopic level and evaluate which PTMs most likely contribute to PF. This paper also reviews the role of novel neo-epitope-specific biomarkers in the early diagnosis and prognosis of fibrotic disorders. We discuss and argue that the altered quality of the individual ECM proteins contributes to the progression of PF and may also lead to the increased quantity of lung proteins. Thus, both quantity and quality appear to be of utmost importance.

AB - 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 focused on the role of protein quantity in relation to the progression of PF, while the importance of lung ECM quality, defined by the levels of ECM protein modifications and by the protein distribution in lung tissue, has not been properly addressed. The quality and function of proteins may be altered by different post-translational modifications (PTMs), such as cross-linking, proteolytic cleavage, citrullination, misfolding and glycosylation. This paper is the first to review key data from the literature related to the lung ECM at the molecular level, relate these to changes observed at a macroscopic level and evaluate which PTMs most likely contribute to PF. This paper also reviews the role of novel neo-epitope-specific biomarkers in the early diagnosis and prognosis of fibrotic disorders. We discuss and argue that the altered quality of the individual ECM proteins contributes to the progression of PF and may also lead to the increased quantity of lung proteins. Thus, both quantity and quality appear to be of utmost importance.

KW - Chronic lung disease

KW - Extracellular matrix

KW - Fibrosis

KW - Idiopathic pulmonary fibrosis

KW - Lung biochemistry

KW - Protein biomarkers

KW - Protein function

KW - Protein structure

U2 - 10.1159/000368163

DO - 10.1159/000368163

M3 - Review

C2 - 25359084

AN - SCOPUS:84927692071

VL - 88

SP - 487

EP - 499

JO - Respiration

JF - Respiration

SN - 0025-7931

IS - 6

ER -