Tranilast inhibits the growth of rat mesangial cells.
We investigated the effects of tranilast on the growth of cultured rat mesangial cells. The number of mesangial cells increased fivefold during a 5-day incubation in RPMI 1640 with 20% fetal bovine serum. The number of cells was significantly lower in the presence of tranilast than in its abscence. Tranilast (0 approximately 500 microM) inhibited platelet-derived growth factor (PDGF)-induced DNA synthesis of rat mesangial cells cultured in RPMI 1640 medium containing 0.5% fetal bovine serum in a dose-dependent manner. The inhibition of DNA synthesis by tranilast was not affected by the presence of indomethacin (1 microg/ml) or N(G)-monomethyl-L-arginine (0.5 mM). Tranilast did not stimulate nitrite oxide synthesis in PDGF-stimulated cells. Mitogen-activated protein kinase activity in mesangial cells was significantly increased by exposure to PDGF, while the effect was significantly suppressed in the presence of tranilast. The present study revealed that tranilast inhibits the growth of rat mesangial cells, independently of nitric oxide or prostacycline synthesis.
Ikeda
M
M
Department of Clinical Immunology, Jichi Medical School, Minamikawachi-Machi, Tochigi, Japan. ikedam@cc.utsunomiya-u.ac.jp
Ikeda
U
U
Shimada
K
K
Fujita
N
N
Okada
K
K
Saito
T
T
Minota
S
S
Kano
S
S
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases; D009569:Nitric Oxide / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D010975:Platelet Aggregation Inhibitors; D062367:ortho-Aminobenzoates; D009569:Nitric Oxide; D011494:Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C012293:tranilast