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Proteases Revisited: Roles and Therapeutic Implications in Fibrosis

Jakub Kryczka1, Joanna Boncela1

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

Mediators of Inflammation
|June 24, 2017
PubMed

Insights

Proteases play a key role in fibrosis by affecting cell migration, tissue remodeling, and inflammatory processes. Understanding protease functions is crucial for developing new anti-fibrotic therapies.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pathology

Background:

  • Proteases are enzymes that break down proteins and are involved in numerous biological processes.
  • Dysregulated protease activity is implicated in various diseases, including fibrosis.
  • Both extracellular and intracellular proteases contribute to cellular functions and disease development.

Purpose of the Study:

  • To review the current knowledge on the role of proteases in fibrosis.
  • To highlight the multidimensional impact of proteases on fibrotic processes.

Main Methods:

  • Literature review of studies on proteases and fibrosis.
  • Analysis of protease functions in relation to cell migration, EMT/EndMT, and ECM remodeling.

Main Results:

  • Extracellular proteases degrade the extracellular matrix (ECM), activate other proteases, disrupt cell junctions, release growth factors (e.g., TGF-β, VEGF), and alter cell mechanosensing.
  • Intracellular proteases, such as caspases and cathepsins, regulate lysosome activity and signal transduction pathways.
  • Protease activity influences cell migration, epithelial-mesenchymal transition (EMT), and endothelial-mesenchymal transition (EndMT), all contributing to fibrosis.

Conclusions:

  • Proteases have a significant and multifaceted role in the development and progression of fibrosis.
  • Targeting specific proteases may offer therapeutic strategies for treating fibrotic diseases.

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