ArticleJournal of immunology (Baltimore, Md. : 1950)2008
CD40-induced signaling in human endothelial cells results in mTORC2- and Akt-dependent expression of vascular endothelial growth factor in vitro and in vivo.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 47 citations in OpenAlex.
- Phase II study of temozolomide (TMZ) and everolimus (RAD001) therapy for metastatic melanoma: a North Central Cancer Treatment Group study, N0675.American journal of clinical oncology · 2014Trial
- Inflammatory response to percutaneous coronary intervention in stable coronary artery disease.Journal of thrombosis and thrombolysis · 2011Trial
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- CD40 Ligand-CD40 Interaction Is an Intermediary between Inflammation and Angiogenesis in Proliferative Diabetic Retinopathy.International journal of molecular sciences · 2023Article
- Multidrug-Loaded Lipid Nanoemulsions for the Combinatorial Treatment of Cerebral Cavernous Malformation Disease.Biomedicines · 2023Article
- The Emerging Role of Branched-Chain Amino Acids in Liver Diseases.Biomedicines · 2022Review
- RETRACTED: The p53-Driven Anticancer Effect ofLife (Basel, Switzerland) · 2022Article
- CREB Coactivator CRTC2 Plays a Crucial Role in Endothelial Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Article
- DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.Physiological reviews · 2018Review
- CD40-mediated HIF-1α expression underlying microangiopathy in diabetic nerve pathology.Disease models & mechanisms · 2018Article
- Semaphorin 3F and Netrin-1: The Novel Function as a Regulator of Tumor Microenvironment.Frontiers in physiology · 2018Review
- Evolving Significance and Future Relevance of Anti-Angiogenic Activity of mTOR Inhibitors in Cancer Therapy.Cancers · 2017Review
- Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation.Circulation research · 2016Article
- Translational implications of endothelial cell dysfunction in association with chronic allograft rejection.Pediatric nephrology (Berlin, Germany) · 2016Review
- Regulation of mTOR Signaling by Semaphorin 3F-Neuropilin 2 Interactions In Vitro and In Vivo.Scientific reports · 2015Article
- Chronic allograft rejection: a fresh look.Current opinion in organ transplantation · 2015Review
- Clinical significance of elevated serum soluble CD40 ligand levels as a diagnostic and prognostic tumor marker for pancreatic ductal adenocarcinoma.Journal of translational medicine · 2014Article
- The relationship between intervention in the CD40 signal pathway and choroidal neovascularization.OncoTargets and therapy · 2014Review
- Targeting the intragraft microenvironment and the development of chronic allograft rejection.Human immunology · 2012Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We have examined CD40-dependent signals in endothelial cells (EC) mediating the expression of vascular endothelial growth factor (VEGF) and VEGF-induced angiogenesis. We treated confluent cultures of EC with soluble CD40L (sCD40L), and by Western blot found a marked increase in the phosphorylation of Akt, 4EBP-1, and S6K1, compared with untreated cells. EC were transfected with a full-length VEGF promoter-luciferase construct and cultured in the absence or presence of rapamycin and sCD40L. We found that rapamycin, which blocks mTORC1 and mTORC2 signaling, inhibited sCD40L-mediated transactivation of VEGF. In addition, by Western blot, we found that the transfection of EC with small interfering RNA (siRNA) to rictor (to inhibit mTORC2), and not raptor (to inhibit mTORC1), inhibited sCD40L-dependent protein expression of VEGF. In additions, we found that basal levels of phosphorylated Akt as well as VEGF were increased in EC transfected with the raptor siRNA. Also, rapamycin failed to inhibit VEGF promoter activation, as well as VEGF protein expression in EC transfected with a constitutively active construct of Akt, further demonstrating that mTORC1 is not necessary for CD40- and Akt-induced expression of VEGF. Finally, we injected human CD40L-transfected fibroblasts or mock transfectants into human skin on SCID mice. We found that the injection of CD40L transfectants, but not mock cells, resulted in VEGF expression and mediated a marked angiogenesis reaction, and this response was reduced in mice treated with rapamycin. Together, these observations indicate that mTORC2 and Akt facilitate CD40-inducible expression of VEGF in EC, which is of clinical importance in tumor growth and the progression of chronic inflammatory diseases.
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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.