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

The International Journal of Biochemistry & Cell Biology
Michael SchuligaDarryl Knight

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 p...Continue Reading

Citations

Feb 14, 2020·PloS One·Katarina ZmajkovicovaJohn Gatfield
Jul 8, 2020·International Journal of Molecular Sciences·Irene RamosDolores Pérez-Sala
Mar 13, 2019·American Journal of Respiratory and Critical Care Medicine·Peter J BarnesLouise E Donnelly
Aug 21, 2019·Cells·Maurizio CammalleriPaola Bagnoli
Sep 4, 2020·Seminars in Thrombosis and Hemostasis·Jecko Thachil, Ton Lisman
Apr 27, 2021·Marine Biotechnology·Kaz KawamuraNoriyuki Satoh
Jun 15, 2021·Seminars in Immunopathology·Chandini RangaswamyThomas Renné
Jun 21, 2020·Drug Discovery Today·Daniele D'AlonzoVincenzo Pavone
Mar 2, 2021·Protein and Peptide Letters·Yi-Shan TangFu Chen

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