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Mediators Inflamm. 2017;2017:2570154. doi: 10.1155/2017/2570154. Epub 2017 May 31.

Proteases Revisited: Roles and Therapeutic Implications in Fibrosis.

Author information

1
Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.

Abstract

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.

PMID:
28642633
PMCID:
PMC5470025
DOI:
10.1155/2017/2570154
[Indexed for MEDLINE]
Free PMC Article

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