Inhibition of platelet-derived growth factor-induced mesangial cell proliferation by cyclooxygenase-2 overexpression is abolished through reactive oxygen species.
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.
Zahner
Gunther
G
Department of Medicine, Division of Nephrology and Osteology, University of Hamburg, Martinistr. 52, 20246 Hamburg, Germany. zahner@uke.uni-hamburg.de
Wolf
Gunter
G
Schroeder
Saskia
S
Stahl
Rolf A K
RA
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2