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Inhibition of platelet‐derived growth factor‐induced mesangial cell proliferation by cyclooxygenase‐2 overexpression is abolished through reactive oxygen species
Author(s) -
Zahner Gunther,
Wolf Gunter,
Schroeder Saskia,
Stahl Rolf A.K.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.03.063
Subject(s) - reactive oxygen species , platelet derived growth factor receptor , cell growth , microbiology and biotechnology , platelet derived growth factor , cyclooxygenase , growth factor , mesangial cell , chemistry , intracellular , cancer research , biology , receptor , biochemistry , enzyme , in vitro
Proliferation of mesangial cells (MC) is an early event in many forms of glomerulonephritis. We have previously shown that platelet‐derived growth factor (PDGF)‐induced proliferation of MC was inhibited by the overexpression of cyclooxygenase‐2 (COX‐2). Since reactive oxygen species (ROS) are important mediators of mitogenic signaling, we evaluated the role of ROS in the COX‐2 induced growth arrest in MC. We demonstrate that ROS are reduced in COX‐2 overexpressing MC. Intracellular elevation of ROS restored PDGF‐induced proliferation, while the expression of the cyclin‐dependent kinase inhibitors p21 cip1 and p27 kip1 were decreased in these cells. The data suggest that COX‐2 decreases ROS formation which consequently leads to the PDGF‐induced inhibition of MC proliferation.