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Title: VEGF induces proliferation, migration, and TGF-{beta}1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinase

Abstract

The role of glomerular endothelial cells in kidney fibrosis remains incompletely understood. While endothelia are indispensable for repair of acute damage, they can produce extracellular matrix proteins and profibrogenic cytokines that promote fibrogenesis. We used a murine cell line with all features of glomerular endothelial cells (glEND.2), which dissected the effects of vascular endothelial growth factor (VEGF) on cell migration, proliferation, and profibrogenic cytokine production. VEGF dose-dependently induced glEND.2 cell migration and proliferation, accompanied by up-regulation of VEGFR-2 phosphorylation and mRNA expression. VEGF induced a profibrogenic gene expression profile, including up-regulation of TGF-{beta}1 mRNA, enhanced TGF-{beta}1 secretion, and bioactivity. VEGF-induced endothelial cell migration and TGF-{beta}1 induction were mediated by the phosphatidyl-inositol-3 kinase pathway, while proliferation was dependent on the Erk1/2 MAP kinase pathway. This suggests that differential modulation of glomerular angiogenesis by selective inhibition of the two identified VEGF-induced signaling pathways could be a therapeutic approach to treat kidney fibrosis.

Authors:
 [1];  [1];  [2];  [1];  [1];  [1];  [1];
  1. Department of Medicine I, University of Erlangen-Nuremberg, Erlangen 91054 (Germany)
  2. Department of Medicine IV, University of Erlangen-Nuremberg, Erlangen 91054 (Germany)
Publication Date:
OSTI Identifier:
20710953
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 334; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2005.07.005; PII: S0006-291X(05)01451-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; FIBROSIS; GENE REGULATION; INHIBITION; INOSITOL; KIDNEYS; LYMPHOKINES; MICE; PHOSPHORYLATION; REPAIR; SECRETION

Citation Formats

Zhaodong, Li, Bork, Jens Peter, Krueger, Bettina, Patsenker, Eleonora, Schulze-Krebs, Anja, Hahn, Eckhart G, Schuppan, Detlef, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, and harvard edu, E-mail: dschuppa@bidmc. VEGF induces proliferation, migration, and TGF-{beta}1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinase. United States: N. p., 2005. Web. doi:10.1016/j.bbrc.2005.07.005.
Zhaodong, Li, Bork, Jens Peter, Krueger, Bettina, Patsenker, Eleonora, Schulze-Krebs, Anja, Hahn, Eckhart G, Schuppan, Detlef, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, & harvard edu, E-mail: dschuppa@bidmc. VEGF induces proliferation, migration, and TGF-{beta}1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinase. United States. https://doi.org/10.1016/j.bbrc.2005.07.005
Zhaodong, Li, Bork, Jens Peter, Krueger, Bettina, Patsenker, Eleonora, Schulze-Krebs, Anja, Hahn, Eckhart G, Schuppan, Detlef, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, and harvard edu, E-mail: dschuppa@bidmc. 2005. "VEGF induces proliferation, migration, and TGF-{beta}1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinase". United States. https://doi.org/10.1016/j.bbrc.2005.07.005.
@article{osti_20710953,
title = {VEGF induces proliferation, migration, and TGF-{beta}1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinase},
author = {Zhaodong, Li and Bork, Jens Peter and Krueger, Bettina and Patsenker, Eleonora and Schulze-Krebs, Anja and Hahn, Eckhart G and Schuppan, Detlef and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 and harvard edu, E-mail: dschuppa@bidmc},
abstractNote = {The role of glomerular endothelial cells in kidney fibrosis remains incompletely understood. While endothelia are indispensable for repair of acute damage, they can produce extracellular matrix proteins and profibrogenic cytokines that promote fibrogenesis. We used a murine cell line with all features of glomerular endothelial cells (glEND.2), which dissected the effects of vascular endothelial growth factor (VEGF) on cell migration, proliferation, and profibrogenic cytokine production. VEGF dose-dependently induced glEND.2 cell migration and proliferation, accompanied by up-regulation of VEGFR-2 phosphorylation and mRNA expression. VEGF induced a profibrogenic gene expression profile, including up-regulation of TGF-{beta}1 mRNA, enhanced TGF-{beta}1 secretion, and bioactivity. VEGF-induced endothelial cell migration and TGF-{beta}1 induction were mediated by the phosphatidyl-inositol-3 kinase pathway, while proliferation was dependent on the Erk1/2 MAP kinase pathway. This suggests that differential modulation of glomerular angiogenesis by selective inhibition of the two identified VEGF-induced signaling pathways could be a therapeutic approach to treat kidney fibrosis.},
doi = {10.1016/j.bbrc.2005.07.005},
url = {https://www.osti.gov/biblio/20710953}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 334,
place = {United States},
year = {Fri Sep 09 00:00:00 EDT 2005},
month = {Fri Sep 09 00:00:00 EDT 2005}
}