title: Angiopoietin-1 inhibits mouse glomerular endothelial cell senescence via Tie2 receptor-modulated ERK1/2 signaling.
abstract: BACKGROUND
  The vasculature plays a key role in the progression of renal damage in aging, with reduction in glomerular and peritubular capillary density and decreased endothelial proliferative response. In this study, we examined the role of angiopoietin-1 (Ang1) in H(2)O(2)-induced senescence in mouse glomerular endothelial cells (MGECs) and the signaling pathway involved.
  
  
  METHODS
  MGECs were subjected to H(2)O(2)-induced senescence, which was evaluated by senescence-associated beta-galactosidase (SA-beta-Gal) staining, cell cycle analysis and expression of p16. Endothelial cell function was assessed by nitric oxide, von Willebrand factor secretion and capillary-like structure formation. Signal transduction was examined by Western blot with or without a specific inhibitor.
  
  
  RESULTS
  Ang1 significantly inhibited H(2)O(2)-induced senescence in MGECs, attenuated SA-beta-Gal activity, resumed growth, and downregulated p16(INK4a) levels. Moreover, Ang1 regulated the secretion and capillary-like structure formation of endothelial cells with aging. However, these changes were markedly blocked by treatment with Ang2, sTie2-Fc and PD98059. Ang1 treatment markedly increased elevated Tie2 and ERK1/2 phosphorylation levels which were reduced by Ang2 and sTie2-Fc. PD98059 substantially reduced senescence while not altering Ang1-stimulated phosphor-Tie2 stimulation.
  
  
  CONCLUSIONS
  The present studies suggest that Ang1 inhibits H(2)O(2)-induced senescence in MGECs via the Ang1-Tie2-ERK1/2 signaling pathway.
authors.affiliation: Huashan Hospital, Institute of Nephrology, Fudan University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Mukherjee
authors.forename: Liyin
authors.initials: L
authors.lastname: Zhang
authors.forename: Shanyan
authors.initials: S
authors.lastname: Lin
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D042787:Receptor, TIE-2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D042787:Receptor, TIE-2; D048052:Mitogen-Activated Protein Kinase 3