Proteases Revisited: Roles and Therapeutic Implications in Fibrosis

Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., pr...

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Main Authors: Jakub Kryczka, Joanna Boncela
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2017/2570154
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author Jakub Kryczka
Joanna Boncela
author_facet Jakub Kryczka
Joanna Boncela
author_sort Jakub Kryczka
collection DOAJ
description Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-β and VEGF), activation of signal proteins and receptors, degradation of inflammatory inhibitors or inflammation-related proteins, and changes in cell mechanosensing and motility. Intracellular proteases, mainly caspases and cathepsins, modulate lysosome activity and signal transduction pathways. Herein, we discuss the current knowledge on the multidimensional impact of proteases on the development of fibrosis.
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series Mediators of Inflammation
spelling doaj-art-d1e2f2622ba142729d76dbd10ba7986e2025-08-20T03:24:02ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/25701542570154Proteases Revisited: Roles and Therapeutic Implications in FibrosisJakub Kryczka0Joanna Boncela1Institute of Medical Biology, Polish Academy of Sciences, Lodz, PolandInstitute of Medical Biology, Polish Academy of Sciences, Lodz, PolandProteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-β and VEGF), activation of signal proteins and receptors, degradation of inflammatory inhibitors or inflammation-related proteins, and changes in cell mechanosensing and motility. Intracellular proteases, mainly caspases and cathepsins, modulate lysosome activity and signal transduction pathways. Herein, we discuss the current knowledge on the multidimensional impact of proteases on the development of fibrosis.http://dx.doi.org/10.1155/2017/2570154
spellingShingle Jakub Kryczka
Joanna Boncela
Proteases Revisited: Roles and Therapeutic Implications in Fibrosis
Mediators of Inflammation
title Proteases Revisited: Roles and Therapeutic Implications in Fibrosis
title_full Proteases Revisited: Roles and Therapeutic Implications in Fibrosis
title_fullStr Proteases Revisited: Roles and Therapeutic Implications in Fibrosis
title_full_unstemmed Proteases Revisited: Roles and Therapeutic Implications in Fibrosis
title_short Proteases Revisited: Roles and Therapeutic Implications in Fibrosis
title_sort proteases revisited roles and therapeutic implications in fibrosis
url http://dx.doi.org/10.1155/2017/2570154
work_keys_str_mv AT jakubkryczka proteasesrevisitedrolesandtherapeuticimplicationsinfibrosis
AT joannaboncela proteasesrevisitedrolesandtherapeuticimplicationsinfibrosis