PPAR‐γ Promotes Endothelial Cell Migration By Inducing the Expression of Sema3g

ABSTRACT In addition to regulating lipid and glucose metabolism, the nuclear receptor PPAR‐γ has emerged as a potentially relevant player in regulating endothelial cell function. Despite the identification of numerous PPAR‐γ targets involved in vascular development, the targets downstream of PPAR‐γ that directly affect endothelial cell function remain to be elucidated. In this report, we identify Sema3g as a novel PPAR‐γ‐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‐γ or PPAR‐γ ligands treatment in human umbilical vein endothelial cells (HUVECs). Chromatin immunoprecipitation (ChIP) and transient transfection assays revealed that PPAR‐γ binds to the Sema3g promoter and activates transcription. Furthermore, we show that overexpression of Sema3g augments PPAR‐γ‐driven HUVECs migration, whereas silencing of Sema3g expression almost completely abrogates PPAR‐γ 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‐γ, which is centrally involved in regulating endothelial cell migration. J. Cell. Biochem. 116: 514–523, 2015. © 2014 Wiley Periodicals, Inc.