ReviewBiology2021
Proteolytic Cleavages in the VEGF Family: Generating Diversity among Angiogenic VEGFs, Essential for the Activation of Lymphangiogenic VEGFs.
Review in Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
30 citing papers in PubMed, 47 citations in OpenAlex.
- Cardiac lymphatic dysfunction and repair in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Structural Basis of Lymphangiogenic Receptor VEGFR-3 Activation Mediated by Distinctive Clustering of the Ligand-Receptor Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Angiogenic Doping: Plausible Yet Difficult to Detect.Sports medicine (Auckland, N.Z.) · 2026Review
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Beyond vessels: unraveling the impact of VEGFs on neuronal functions and structure.Journal of biomedical science · 2025Review
- Characterization of hepatocarcinoma cells: lymphatic metastasis potential through enhanced production, expression, and secretion along the VEGF-C/D-VEGFR-3/NRP-2 axis.Discover oncology · 2025Article
- Insulin Receptor Substrate-2 Regulates the Secretion of Growth Factors in Response to Amino Acid Deprivation.International journal of molecular sciences · 2025Article
- Neutrophils in tumor- and inflammation-induced lymphangiogenesis.International journal of biological sciences · 2025Review
- Molecular and Cellular Machinery of Lymphatic Metastasis in Breast Cancer.OncoTargets and therapy · 2025Review
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Molecular Characterization and Interaction between Human VEGF-D and VEGFR-3.Journal of microbiology and biotechnology · 2024Article
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- Apelin-VEGF-C mRNA delivery as therapeutic for the treatment of secondary lymphedema.EMBO molecular medicine · 2024Article
- Biology and therapeutic targeting of vascular endothelial growth factor A.Nature reviews. Molecular cell biology · 2023Review
- Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors.International journal of molecular sciences · 2023Review
- Article
- The emerging roles of long noncoding RNAs in lymphatic vascular development and disease.Cellular and molecular life sciences : CMLS · 2023Review
- Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea.Cells · 2023Review
- Article
- Reprogramming of sentinel lymph node microenvironment during tumor metastasis.Journal of biomedical science · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph-angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. At least five different proteases mediate the activating cleavage of VEGF-C: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the "mature" growth factors, which differ in affinity and receptor activation potential. The "default" VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D, and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by distinct proteases. During embryonic development, ADAMTS3 activates VEGF-C. The other activating proteases are likely important for non-developmental lymphangiogenesis during, e.g., tissue regeneration, inflammation, immune response, and pathological tumor-associated lymphangiogenesis. The better we understand these events at the molecular level, the greater our chances of developing successful therapies targeting VEGF-C and VEGF-D for diseases involving the lymphatics such as lymphedema or cancer.
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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.