ArticleJournal of cellular and molecular medicine2019
Engineering of TIMP-3 as a LAP-fusion protein for targeting to sites of inflammation.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Pooled it
- Targeting Aggrecanases for Osteoarthritis Therapy: From Zinc Chelation to Exosite Inhibition.Journal of medicinal chemistry · 2022Review
- TIMP3 involvement and potentiality in the diagnosis, prognosis and treatment of diabetic nephropathy.Acta diabetologica · 2021Review
- Targeting Cartilage Degradation in Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Restoration of renal TIMP3 levels via genetics and pharmacological approach prevents experimental diabetic nephropathy.Clinical and translational medicine · 2021Article
- Tissue inhibitor of matrix metalloproteinase-3 has both anti-metastatic and anti-tumourigenic properties.Clinical & experimental metastasis · 2020Review
- Biology of Tissue Inhibitor of Metalloproteinase 3 (TIMP3), and Its Therapeutic Implications in Cardiovascular Pathology.Frontiers in physiology · 2020Review
- Engineering of TIMP-3 as a LAP-fusion protein for targeting to sites of inflammation.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue inhibitor of metalloproteinase (TIMP)-3 is a natural inhibitor of a range of enzymes that degrade connective tissue and are involved in the pathogenesis of conditions such as arthritis and cancer. We describe here the engineering of TIMP-3 using a novel drug-delivery system known as the 'LAP technology'. This involves creating therapeutic proteins in fusion with the latency-associated peptide (LAP) from the cytokine TGF-? to generate proteins that are biologically inactive until cleavage of the LAP to release the therapy. LAP-TIMP-3 was successfully expressed in mammalian cells and the presence of the LAP resulted in a 14-fold increase in the quantity of recombinant TIMP-3 produced. LAP-TIMP-3 was latent until release from the LAP by treatment with matrix metalloproteinase when it could inhibit proteases of the adamalysins and adamalysins with thrombospondin motifs families, but not matrix metalloproteinases, indicating that this version of TIMP-3 is a more specific inhibitor than the native protein. There was sufficient protease activity in synovial fluid from human joints with osteoarthritis to release TIMP-3 from the LAP fusion. These results demonstrate the potential for development of TIMP-3 as a novel therapy for conditions where upregulation of catabolic enzymes are part of the pathology.
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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.