SOCS3 is an endogenous inhibitor of pathologic angiogenesis

作者：Stahl Andreas; Joyal Jean Sebastian; Chen Jing; Sapieha Przemyslaw; Juan Aimee M; Hatton Colman J; Pei Dorothy T; Hurst Christian G; Seaward Molly R; Krah Nathan M; Dennison Roberta J; Greene Emily R; Boscolo Elisa; Panigrahy Dipak; Smith Lois E H^*

来源：Blood, 2012, 120(14): 2925-2929.

DOI：10.1182/blood-2012-04-422527

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 TNF alpha 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. (Blood. 2012; 120(14): 2925-2929)

• 出版日期2012-10-4