Cysteine cathepsins in extracellular matrix remodeling: Extracellular matrix degradation and beyond
Abstract
Cysteine cathepsins have been for a long time considered to execute mainly nonspecific bulk proteolysis in the endolysosomal system. However, this view has been changing profoundly over the last decade as cathepsins were found in the cytoplasm, nucleus and in the extracellular milieu. Cathepsins are currently gaining increased attention largely because of their extracellular roles associated with disease development and progression. While kept under tight control under physiological conditions, their dysregulated and elevated activity in the extracellular milieu are distinctive hallmarks of numerous diseases such as various cancers, inflammatory disorders, rheumatoid arthritis, bone disorders and heart diseases. In this review, we discuss cysteine cathepsins with a major focus on their extracellular roles and extracellular proteolytic targets beyond degradation of the extracellular matrix. We further highlight the perspectives of cathepsin research and novel avenues in cathepsin-based diagnostic and therapeutic applications.
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Reduced AP-1 activates TIMP-1 gene expression.
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From An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth (2019) · cites this paper as [50]
As a result, collagen accumulates in ECM and causes gingival overgrowth.
“As a result of this, collagen accumulates in ECM and causes gingival overgrowth [44, 49, 50].”
From An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth (2019) · cites this paper as [50]
Phenytoin decreases MMP-1 by increasing the expression of TIMP-1.
“The result is that phenytoin decreases the MMP-1 by increasing the expression of TIMP-1.”
From An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth (2019) · cites this paper as [50]
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“They are involved in various cellular processes, such as protein turnover, antigen presentation, apoptosis, and matrix remodeling (Fonović and Turk, 2014; Turk et al., 2000, 2012; Vizovišek et al., 2019).”
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“These proteinases target a wide range of ECM proteins, such as collagen, laminin and elastin (Lu et al. 2011; Vizovišek et al., 2019), almost all of which were depleted in tumour samples.”
BackgroundA humanized antibody inhibitor for cathepsin L
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- Authors
- Vizovišek, M., Fonović, M., & Turk, B.
- Affiliations
- Jožef Stefan Institute (SI)
- University of Ljubljana (SI)
- Corresponding author
- Turk, Boris
- Venue
- Matrix Biology
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 75-76
- Pages
- 141-159
- ISSN
- 0945-053X (ISSN-L)
- OpenAlex
- W2791144662
- Cited by
- 200
- References
- 0
- Citations by year
- 2026: 22 · 2025: 26 · 2024: 26 · 2023: 31 · 2022: 21 · 2021: 19 · 2020: 35 · 2019: 19 · 2018: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Matrix Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Slovenian Research Agency (P1-0140, N1-022)
- ICGEB (CRP/SVN16-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Keywords
- cysteine cathepsins, extracellular matrix remodeling, extracellular matrix degradation, extracellular proteolysis, cancer, rheumatoid arthritis, bone disease, heart disease, inflammatory diseases
- MeSH terms
- Arthritis, Rheumatoid, Cathepsins, Cysteine, Cysteine Endopeptidases, Extracellular Matrix, Heart Diseases, Humans, Inflammation, Lysosomes, Neoplasms, Proteolysis
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