title: Low grade inflammation inhibits VEGF induced HUVECs migration in p53 dependent manner.
abstract: In the course of studying crosstalk between inflammation and angiogenesis, high doses of pro-inflammatory factors have been reported to induce apoptosis in cells. Under normal circumstances also the pro-inflammatory cytokines are being released in low doses and are actively involved in cell signaling pathways. We studied the effects of low grade inflammation in growth factor induced angiogenesis using tumor necrosis factor alfa (TNFα) and vascular endothelial growth factor A (VEGF) respectively. We found that low dose of TNFα can inhibit VEGF induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Low dose of TNFα induces mild upregulation and moreover nuclear localization of tumor suppressor protein 53 (P53) which causes decrease in inhibitor of DNA binding-1 (Id1) expression and shuttling to the cytoplasm. In absence of Id1, HUVECs fail to upregulate β3-integrin and cell migration is decreased. Connecting low dose of TNFα induced p53 to β3-integrin through Id1, we present additional link in cross talk between inflammation and angiogenesis.
authors.affiliation: Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
authors.forename: Sushil
authors.initials: S
authors.lastname: Panta
authors.affiliation: Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Japan; Kagoshima University Hospital, Kagoshima, Japan. Electronic address: munekazu@m.kufm.kagoshima-u.ac.jp.
authors.forename: Munekazu
authors.initials: M
authors.lastname: Yamakuchi
authors.affiliation: Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Takenouchi
authors.affiliation: Kagoshima University Hospital, Kagoshima, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Oyama
authors.affiliation: Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Japan; Kagoshima University Hospital, Kagoshima, Japan.
authors.forename: Toyoyasu
authors.initials: T
authors.lastname: Koriyama
authors.affiliation: Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Japan; Kagoshima University Hospital, Kagoshima, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kojo
authors.affiliation: Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Japan; Kagoshima University Hospital, Kagoshima, Japan. Electronic address: terutoha@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Teruto
authors.initials: T
authors.lastname: Hashiguchi
mesh_terms: D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C497453:ID1 protein, human; C061248:ITGB3 protein, human; D051798:Inhibitor of Differentiation Protein 1; D039661:Integrin beta3; C439524:TNF protein, human; C495901:TP53 protein, human; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Endothelial migration; Id1; P53; TNFα; VEGF; β(3)-integrin