title: 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.
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.forename: Jingjin
authors.initials: J
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D042783:Endothelial Cells / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D047495:PPAR gamma / Q000819:agonists*; D011401:Promoter Regions, Genetic; D000077154:Rosiglitazone; D039961:Semaphorins / Q000235:genetics* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D047495:PPAR gamma; D039961:Semaphorins; D045162:Thiazolidinediones; C569384:semaphorin 3G, human; D000077154:Rosiglitazone
keywords: ENDOTHELIAL CELL; MIGRATION; PPAR-γ; Semaphorin3g; TRANSACTIVATION