Cited by 144Cytokine Signaling Pathways and InteractionsAngiogenesis and VEGF in CancerLymphatic System and Diseases

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In vivo activation of JAK2/STAT‐3 pathway during angiogenesis induced by GM‐CSF

Valdembri, Donatella, Serini, Guido, Vacca, Angelo, Ribatti, Domenico, Bussolino, Federico·2002·The FASEB Journal

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Abstract

Besides the regulation of hematopoiesis, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) induces the expression of a functional program in cultured endothelial cells (ECs) related to angiogenesis and to the their survival in bone marrow microenvironment. ECs express the specific GM‐CSF receptor that signals through the recruitment and the activation of Janus kinase (JAK)2 (Soldi et al., Blood 89 , 863–872, 1987). We now report that GM‐CSF in vivo induces angiogenesis and activates JAK‐2 and signal transducers and activators of transcription (STAT)‐3. This cytokine has an angiogenetic activity in chick chorioallantoic membrane (CAM) without recruitment of inflammatory cells and induces vessel sprouting from chicken aorta rings. When added to CAM, subnanomolar concentrations of GM‐CSF cause a rapid phosphorylation in tyrosine residues of JAK‐2 persisting at least for 10 min. Furthermore, we show that signal transducers and activators of transcription (STAT)‐3, but not STAT‐5, also are phosphorylated for 30 min after GM‐CSF stimulation. AG‐490, a JAK‐2 inhibitor, reduced in a dose‐dependent manner the angiogenic effect of GM‐CSF in CAM. These findings provide the first evidence that the JAK‐2/STAT‐3 pathway is activated in vivo and participates in vessel formation triggered by GM‐CSF.

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Authors: Valdembri, D., Serini, G., Vacca, A., Ribatti, D., & Bussolino, F.
Affiliations: University of Turin (IT)
University of Bari Aldo Moro (IT)
Department of Human Anatomy and Histology University of Bari Bari Italy
ORCID: Valdembri, Donatella
Serini, Guido
Vacca, Angelo
Bussolino, Federico
Venue: The FASEB Journal
Publisher: Wiley
Published: 2001-12-14
Volume: 16
Issue: 2
Pages: 1-19
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.01-0633fje
OpenAlex: W1964106770
Cited by: 144
References: 69
Citations by year: 2026: 3 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 8 · 2017: 2 · 2016: 2 · 2015: 9 · 2014: 8 · 2013: 7 · 2012: 6
FWCI: 3.40
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
Funders: Associazione Italiana per la Ricerca sul Cancro
Istituto Superiore di Sanità
Associazione Italiana per la Lotta al Neuroblastoma
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
Keywords: GM-CSF, JAK2/STAT3 signaling, angiogenesis, endothelial cells, JAK2 phosphorylation, STAT3 phosphorylation, STAT5, AG490, JAK2 inhibitors, chorioallantoic membrane, vessel sprouting, bone marrow microenvironment, endothelial cell survival
MeSH terms: Allantois, Animals, Aorta, Blood Vessels, Chick Embryo, Chickens, Chorion, DNA-Binding Proteins, Endothelium, Vascular, Phosphorylation, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Tyrosine, Signal Transduction, Trans-Activators, Granulocyte-Macrophage Colony-Stimulating Factor, Neovascularization, Physiologic, STAT3 Transcription Factor, Janus Kinase 2

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In vivo activation of JAK2/STAT‐3 pathway during angiogenesis induced by GM‐CSF

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