SOCS3 is an endogenous inhibitor of pathologic angiogenesis
| Autor: | Elisa Boscolo, Nathan M. Krah, Aimee M. Juan, Dorothy T. Pei, Przemyslaw Sapieha, Christian G. Hurst, Molly R. Seaward, Emily R. Greene, Jean-Sebastian Joyal, Jing Chen, Dipak Panigrahy, Andreas Stahl, Lois E.H. Smith, Roberta J. Dennison, Colman J. Hatton |
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| Rok vydání: | 2012 |
| Předmět: |
biology
Angiogenesis medicine.medical_treatment Growth factor digestive oral and skin physiology Immunology Cell Biology Hematology Biochemistry Proinflammatory cytokine Neovascularization Cytokine Vascular Biology biology.protein Cancer research medicine SOCS3 medicine.symptom STAT3 PI3K/AKT/mTOR pathway |
| Zdroj: | Blood. 120:2925-2929 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Inflammatory cytokines and growth factors drive angiogenesis independently; however, their integrated role in pathologic and physiologic angiogenesis is not fully understood. Suppressor of cytokine signaling-3 (SOCS3) is an inducible negative feedback regulator of inflammation and growth factor signaling. In the present study, we show that SOCS3 curbs pathologic angiogenesis. Using a Cre/Lox system, we deleted SOCS3 in vessels and studied developmental and pathologic angiogenesis in murine models of oxygen-induced retinopathy and cancer. Conditional loss of SOCS3 leads to increased pathologic neovascularization, resulting in pronounced retinopathy and increased tumor size. In contrast, physiologic vascularization is not regulated by SOCS3. In vitro, SOCS3 knockdown increases proliferation and sprouting of endothelial cells costimulated with IGF-1 and TNFα via reduced feedback inhibition of the STAT3 and mTOR pathways. These results identify SOCS3 as a pivotal endogenous feedback inhibitor of pathologic angiogenesis and a potential therapeutic target acting at the converging crossroads of growth factor– and cytokine-induced vessel growth. |
| Databáze: | OpenAIRE |
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