Anti-SEMA3G (full length) polyclonal antibody

In addition to regulating lipid and glucose metabolism, the nuclear receptor PPAR- has emerged as a potentially relevant player in regulating endothelial cell function. Despite the identification of numerous PPAR- targets involved in vascular development, the targets downstream of PPAR- that directly affect endothelial cell function remain to be elucidated. In this report, we identify Sema3g as a novel PPAR--regulated gene playing a substantial role in endothelial biology, particularly with respect to endothelial cell migration. Sema3g expression is induced by either overexpression of PPAR- or PPAR- ligands treatment in human umbilical vein endothelial cells (HUVECs). Chromatin immunoprecipitation (ChIP) and transient transfection assays revealed that PPAR- binds to the Sema3g promoter and activates transcription. Furthermore, we show that overexpression of Sema3g augments PPAR--driven HUVECs migration, whereas silencing of Sema3g expression almost completely abrogates PPAR- or Sema3g-mediated cell migration. Accordingly, the anti-neuropilin-2 (Sema3g receptor) neutralizing antibody treatment markedly inhibits Sema3g-induced cell migration. Collectively, these results identify Sema3g as one of the downstream effectors of PPAR-, which is centrally involved in regulating endothelial cell migration. J. Cell. Biochem. 116: 514-523, 2015. (c) 2014 Wiley Periodicals, Inc.

Class-3 semaphorins are secreted axon guidance factors. Some of these semaphorins have recently been characterized as suppressors of tumor progression. To determine if class-3 semaphorins can be used to inhibit the development of glioblastoma-multiforme tumors, we expressed recombinant sema-3A, 3B, 3D, 3E, 3F or 3G in U87MG glioblastoma cells. Sema3A and sema3B expressing cells contracted and changed shape persistently while cells expressing other semaphorins did not. Sema3A and sema3F differed from other semaphorins including sema3B as they also inhibited the proliferation of the cells and the formation of soft agar colonies. With the exception of sema3G and sema3B, expression of these semaphorins in U87MG cells inhibited significantly tumor development from subcutaneously implanted cells. Strong inhibition of tumor development was also observed following implantation of U87MG cells expressing each of the class-3 semaphorins in the cortex of mouse brains. Sema3D and sema3E displayed the strongest inhibitory effects and their expression in U373MG or in U87MG glioblastoma cells implanted in the brains of mice prolonged the survival of the mice by more then two folds. Furthermore, most of the mice that died prior to the end of the experiment did not develop detectable tumors and many of the mice survived to the end of the experiment. Most of the semaphorins that we have used here with the exception of sema3D were characterized previously as inhibitors of angiogenesis. Our results indicate that sema3D also functions as an inhibitor of angiogenesis and suggest that the anti-tumorigenic effects are due primarily to inhibition of tumor angiogenesis. These results indicate that class-3 semaphorins such as sema3D and sema3E could perhaps be used to treat glioblastoma patients.