Renal and Clinical Biochemistry Research Laboratories , School of Postgraduate Medicine , University of Keele , North Staffordshire Hospital Centre , Stoke on Trent , UK .
Nephron 72 : 263-8 ( 1996)
Abstract
This study indirectly examined the role of prostanoids ( PG ) in mediating rat mesangial cell ( MC ) DNA synthesis induced by hydrogen peroxide ( H2O2 ) , interleukin 6 ( IL-6 ) , and platelet-derived growth factor ( PDGF ) .
MC were exposed to three daily pulses of 10(-6 ) mol/l H2O2 alone or in combination with IL-6 ( 5 ng/ml ) or PDGF ( 10 ng/ml ) .
In order to examine ( indirectly ) the role of PG in mediating changes in MC DNA synthesis , indomethacin ( 1.5 x 10(-5 ) mol/l ) or the thromboxane A2 synthetase inhibitor Dazmegrel ( 10(-5 ) mol/l ) was added to the medium and DNA synthesis assessed after 72 h using 3H-thymidine incorporation ( 3H-TdR ) .
Stimulation of MC by H2O2 alone resulted in an increase in H-TdR of 34.7 +/- 5.5% ( p < ; 0.01 ) .
H2O2 enhanced the mitogenic effects of IL-6 and PDGF , 3H-TdR increasing by 52 +/- 12.1% ( p < ; 0.01 ) and 100 +/- 21% ( p < ; 0.001 ) , respectively .
Indomethacin suppressed the DNA synthesis induced by H2O2 alone , 3H-TdR decreasing by 33 +/- 12% ( p < ; . 05 ) .
Indomethacin also reduced the mitogenic response to H2O2 plus IL-6 and H2O2 plus PDGF by 91 +/- 17 and 97 +/- 12% , respectively ( p < ; . 05 ) .
Dazmegrel reduced 3H-TdR when MC were exposed to H2O2 alone by . 8 +/- 16% ( p < ; 0.05 ) and when combined with IL-6 or PDGF by 80 +/- 26 and 120 +/- 13% , respectively ( p < ; 0.05 ) .
These data suggest that the pathways through which H2O2-induced growth of MC is mediated appear , at least in part , to involve PG , particularly thromboxane A2 .