Affordable Access

deepdyve-link
Publisher Website

The fibrogenic actions of the coagulant and plasminogen activation systems in pulmonary fibrosis.

Authors
  • Schuliga, Michael1
  • Grainge, Christopher2
  • Westall, Glen3
  • Knight, Darryl4
  • 1 School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia. Electronic address: [email protected] , (Australia)
  • 2 Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia. , (Australia)
  • 3 Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Prahran, Victoria, Australia. , (Australia)
  • 4 School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia; Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Canada. , (Australia)
Type
Published Article
Journal
The international journal of biochemistry & cell biology
Publication Date
Apr 01, 2018
Volume
97
Pages
108–117
Identifiers
DOI: 10.1016/j.biocel.2018.02.016
PMID: 29474926
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fibrin formation in the intra-alveolar compartment is postulated to have a pivotal role in the development of pulmonary fibrosis, serving as a provisional matrix for migrating fibroblasts. Furthermore, proteases of the coagulation and plasminogen activation (plasminergic) systems that form and breakdown fibrin respectively directly contribute to pulmonary fibrosis. The coagulants, thrombin and factor Xa (FXa) evoke fibrogenic effects via cleavage of the N-terminus of protease-activated receptors (PARs). Whilst the formation and activity of plasmin, the principle plasminergic mediator is suppressed in the airspaces of patients with IPF, localized increases are likely to occur in the lung interstitium. Plasmin-evoked proteolytic activation of factor XII (FXII), matrix metalloproteases (MMPs) and latent, matrix-bound growth factors such as epidermal growth factor (EGF) indirectly implicate plasmin in pulmonary fibrosis. Another plasminergic protease, urokinase plasminogen activator (uPA) is associated with regions of fibrosis in the remodelled lung of IPF patients and elicits fibrogenic activity via binding its receptor (uPAR). Plasminogen activator inhibitor-1 (PAI-1) formed in the injured alveolar epithelium also contributes to pulmonary fibrosis in a manner that involves vitronectin binding. This review describes the mechanisms by which components of the two systems primarily involved in fibrin homeostasis contribute to interstitial fibrosis, with a particular focus on IPF. Selectively targeting the receptor-mediated mechanisms of coagulant and plasminergic proteases may limit pulmonary fibrosis, without the bleeding complications associated with conventional anti-coagulant and thrombolytic therapies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Report this publication

Statistics

Seen <100 times