ArticleBlood2012
Antagonism of VEGF-A-induced increase in vascular permeability by an integrin α3β1-Shp-1-cAMP/PKA pathway.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 50 citations in OpenAlex.
- VEGF-B-mediated myofiber types involved in high-fat diet-induced hyperglycemia through PKA-NFATs signaling pathway.Stem cell research & therapy · 2025Article
- Hypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue of male mice.Nature communications · 2024Article
- TIMP2 ameliorates blood-brain barrier disruption in traumatic brain injury by inhibiting Src-dependent VE-cadherin internalization.The Journal of clinical investigation · 2023Article
- The Continuing Saga of Tissue Inhibitor of Metalloproteinase 2: Emerging Roles in Tissue Homeostasis and Cancer Progression.The American journal of pathology · 2023Review
- The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence.Cell biology and toxicology · 2023Article
- Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- Fibroblasts repair blood-brain barrier damage and hemorrhagic brain injury via TIMP2.Cell reports · 2022Article
- Broussonin A- and B-mediated inhibition of angiogenesis by blockade of VEGFR-2 signalling pathways and integrin β1 expression.Journal of cellular and molecular medicine · 2022Article
- The lncRNA-miRNA-integrin alpha V ceRNA network can affect the occurrence and prognosis of gastric cancer.International journal of clinical and experimental pathology · 2022Article
- TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer.Carcinogenesis · 2020Article
- Novel functions for 2-phenylbenzimidazole-5-sulphonic acid: Inhibition of ovarian cancer cell responses and tumour angiogenesis.Journal of cellular and molecular medicine · 2020Article
- MicroRNA-130b functions as an oncomiRNA in non-small cell lung cancer by targeting tissue inhibitor of metalloproteinase-2.Scientific reports · 2019Article
- The Many Facets of Metzincins and Their Endogenous Inhibitors: Perspectives on Ovarian Cancer Progression.International journal of molecular sciences · 2018Review
- Cgnl1, an endothelial junction complex protein, regulates GTPase mediated angiogenesis.Cardiovascular research · 2017Article
- Annexin A2 supports pulmonary microvascular integrity by linking vascular endothelial cadherin and protein tyrosine phosphatases.The Journal of experimental medicine · 2017Article
- Article
- Peripheral blood AKAP7 expression as an early marker for lymphocyte-mediated post-stroke blood brain barrier disruption.Scientific reports · 2017Article
- Blood Brothers: Hemodynamics and Cell-Matrix Interactions in Endothelial Function.Antioxidants & redox signaling · 2016Review
- Engineering pulmonary vasculature in decellularized rat and human lungs.Nature biotechnology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
In cancer, VEGF-induced increase in vascular permeability results in increased interstitial pressure, reducing perfusion and increasing hypoxia, which reduce delivery of chemotherapeutic agents and increase resistance to ionizing radiation. Here, we show that both TIMP-2 and Ala + TIMP-2, a TIMP-2 mutant without matrix metalloproteinase inhibitory activity, antagonize the VEGF-A-induced increase in vascular permeability, both in vitro and in vivo. Like other agents known to preserve endothelial barrier function, TIMP-2 elevates cytosolic levels of cAMP and increases cytoskeletal-associated vascular endothelial cadherin in human microvascular endothelial cells. All of these effects are completely ablated by selective knockdown of integrin α3β1 expression, expression of a dominant negative protein tyrosine phosphatase Shp-1 mutant, administration of the protein tyrosine phosphatase inhibitor orthovanadate, or the adenylate cyclase inhibitor SQ22536. This TIMP-2-mediated inhibition of vascular permeability involves an integrin α3β1-Shp-1-cAMP/protein kinase A-dependent vascular endothelial cadherin cytoskeletal association, as evidenced by using siRNAs to integrin α3β1 and Shp-1, or treatment with Shp-1 inhibitor NSC87877 and protein kinase A inhibitor H89. Our results demonstrate the potential utility for TIMP-2 in cancer therapy through "normalization" of vascular permeability in addition to previously described antiangiogenic effects.
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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.