ArticlePloS one2012
Granzyme B cleaves decorin, biglycan and soluble betaglycan, releasing active transforming growth factor-β1.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 66 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 104 citations in OpenAlex.
- Granzyme B in age-related macular degeneration: mechanistic insights and therapeutic perspectives.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Emerging roles of granzymes in neurodegeneration and neuroinflammation: mechanistic insights and therapeutic opportunities.Acta neuropathologica · 2026Review
- Role of Notch signaling in corticalization.Journal of endocrinological investigation · 2026Review
- Granzyme B contributes to subretinal fibrosis in neovascular age-related macular degeneration by modulating inflammation and epithelial-mesenchymal transition.Journal of neuroinflammation · 2025Article
- NK cell activity in the tumor microenvironment.Frontiers in cell and developmental biology · 2025Review
- Granzyme B cleaves tenascin-C to release its C-terminal domain in rheumatoid arthritis.JCI insight · 2024Article
- Granzyme B degrades extracellular matrix and promotes inflammation and choroidal neovascularization.Angiogenesis · 2024Article
- Article
- Granzyme serine proteases in inflammation and rheumatic diseases.Nature reviews. Rheumatology · 2024Review
- Functionalised biomaterials as synthetic extracellular matrices to promote vascularisation and healing of diabetic wounds.Cell and tissue research · 2024Review
- Serum decorin and biglycan levels as predictive biomarkers for lung fibrosis severity and mortality risk in COVID-19 patients.Frontiers in medicine · 2024Article
- Potential implications of granzyme B in keloids and hypertrophic scars through extracellular matrix remodeling and latent TGF-β activation.Frontiers in immunology · 2024Article
- Exploring the role of granzyme B in subretinal fibrosis of age-related macular degeneration.Frontiers in immunology · 2024Review
- Small leucine rich proteoglycans: Biology, function and their therapeutic potential in the ocular surface.The ocular surface · 2023Review
- Lower Circulating Cytotoxic T-Cell Frequency and Higher Intragraft Granzyme-B Expression Are Associated with Inflammatory Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Recipients.Medicina (Kaunas, Lithuania) · 2023Article
- Granzyme B in Autoimmune Skin Disease.Biomolecules · 2023Review
- Proteolysis: a key post-translational modification regulating proteoglycans.American journal of physiology. Cell physiology · 2022Review
- Porcine intraepithelial lymphocytes undergo migration and produce an antiviral response following intestinal virus infection.Communications biology · 2022Article
- Potential role of extracellular granzyme B in wet age-related macular degeneration and fuchs endothelial corneal dystrophy.Frontiers in pharmacology · 2022Review
- Granzyme B mediates impaired healing of pressure injuries in aged skin.NPJ aging and mechanisms of disease · 2021Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveGranzyme B (GrB) is a pro-apoptotic serine protease that contributes to immune-mediated target cell apoptosis. However, during inflammation, GrB accumulates in the extracellular space, retains its activity, and is capable of cleaving extracellular matrix (ECM) proteins. Recent studies have implicated a pathogenic extracellular role for GrB in cardiovascular disease, yet the pathophysiological consequences of extracellular GrB activity remain largely unknown. The objective of this study was to identify proteoglycan (PG) substrates of GrB and examine the ability of GrB to release PG-sequestered TGF-β1 into the extracellular milieu. METHODS/
resultsThree extracellular GrB PG substrates were identified; decorin, biglycan and betaglycan. As all of these PGs sequester active TGF-β1, cytokine release assays were conducted to establish if GrB-mediated PG cleavage induced TGF-β1 release. Our data confirmed that GrB liberated TGF-β1 from all three substrates as well as from endogenous ECM and this process was inhibited by the GrB inhibitor 3,4-dichloroisocoumarin. The released TGF-β1 retained its activity as indicated by the induction of SMAD-3 phosphorylation in human coronary artery smooth muscle cells.
conclusionIn addition to contributing to ECM degradation and the loss of tissue structural integrity in vivo, increased extracellular GrB activity is also capable of inducing the release of active TGF-β1 from PGs.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.