SOCS3 regulates vascular sprouting and endothelial activation. (A) Schematic representation of the signaling pathways regulated by SOCS3. (B) Increased sprouting of TNFα/IGF-1–stimulated aortic rings from Tie2-Socs3^ko compared with Socs3^flox/flox mice (n = 4-6). (C) Increased proliferation of human ECs treated with SOCS3 siRNA compared with controls (n = 9-10). (D) Expression of phospho-mTOR (P-mTOR) and P-STAT3 (green) in neovascular tufts (NV, red) of the OIR retina of Tie2-Socs3^ko (not shown) and Socs3^flox/flox control mice (n = 4). GCL indicates ganglion cell layer; INL, inner nuclear layer; and ONL, outer nuclear layer. (E) Increased mTOR and STAT3 phosphorylation, but not ERK, in IGF-1–stimulated ECs treated with Socs3 siRNA compared with controls (n = 3-5). (F) Prestimulation with TNFα (15 minutes) before IGF-1 further pronounces the increase of P-mTOR and P-STAT3 in IGF-1–stimulated ECs treated with Socs3 siRNA compared with controls (n = 3-6). Scale bar in panel B indicates 1 mm; and panel D, 50 μm. NS indicates not significant, *P < .05, **P < .01.