title: AP-1 transcription factor mediates VEGF-induced endothelial cell migration and proliferation.
abstract: VEGF, upon binding to its endothelial cell specific receptors VEGF-R1 and VEGF-R2, can induce endothelial cell migration, proliferation and angiogenesis. However, the molecular mechanism of these effects still remains unclear. In this study, we investigated whether VEGF promotes human umbilical vascular endothelial cell (HUVEC) migration and proliferation through activator protein-1 transcription factor (AP-1) family. We first showed that VEGF induces immediate-early genes AP-1 family gene expression differentially with the profound induction of JunB (both mRNA and protein) under various conditions (PBS, DMSO or control adenoviruses). The increase in AP-1 mRNA expression occurs primarily at the transcriptional level. Inhibition of AP-1 DNA binding activity by adenovirus expressing a potent dominant negative form of c-Fos (Afos) significantly attenuated VEGF-induced HUVEC migration and proliferation and cyclin D1 expression. Knockdown of JunB with adenovirus expressing JunB shRNA reduces VEGF-induced JunB expression and attenuated HUVEC migration. However the shJunB-expressing virus has no effect on VEGF-induced cyclin D1 protein expression and proliferation. These results suggest that VEGF-induced endothelial migration is mediated primarily by induction of JunB whereas the promotion of endothelial proliferation by VEGF is mediated by JunB-independent AP-1 family members.
authors: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA; School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China.
authors: Jing
authors: J
authors: Jia
authors: Divison of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA; Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors: Taiyang
authors: T
authors: Ye
authors: Divison of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA; Department of General Surgery, Pancreatic Disease Institute, Union Hospital, Huazhong University of Science & Technology, Wuhan, China.
authors: Pengfei
authors: P
authors: Cui
authors: School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China.
authors: Qian
authors: Q
authors: Hua
authors: Divison of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA.
authors: Huiyan
authors: H
authors: Zeng
authors: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02460, USA. Electronic address: dzhao@bidmc.harvard.edu.
authors: Dezheng
authors: D
authors: Zhao
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: C530104:CCND1 protein, human; C581727:JunB protein, human; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1
keywords: AP-1; Angiogenesis; Endothelial cells; VEGF