Effects of endogenously produced arachidonic acid metabolites on rat mesangial cell proliferation.
The role of endogenously produced arachidonic acid metabolites on glomerulonephritis was investigated using cultured rat mesangial cells. The cultured mesangial cells could produce prostaglandin (PG) E2 and F2 alpha and 12-hydroxyeicosatetraenoic acid (12-HETE). The treatment of the mesangial cells with indomethacin enhanced the cell growth stimulated by 10% fetal calf serum (FCS). This stimulatory effect was significantly attenuated by concomitant treatment with PGE2, but not with PGF2 alpha. To test whether the mechanism by which PGE2 inhibited the mesangial cell growth is related to in the increment of cyclic AMP (cAMP), we examined the effect of dibutyryl cAMP on mesangial cell growth. As expected, treatment with dibutyryl cAMP decreased the cell proliferation. Moreover treatment with KT-5720, a protein kinase A (PKA) inhibitor, stimulated the cell growth as well as indomethacin. These data strongly suggest that the inhibition of mesangial cell growth by PGE2 involves an activation of PKA. In contrast, treatment with baicalein, a specific inhibitor of 12-lipoxygenase, inhibited the mesangial cell growth. The up and down regulations by arachidonic acid metabolites were also observed in the growth induced by platelet-derived growth factor (PDGF). These results suggest that endogenously produced arachidonic acid metabolites are involved in the regulation of mesangial cell growth.
Nakahama
K
K
Department of Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Japan.
Morita
I
I
Murota
S
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D044482:Benzeneacetamides; D003994:Bucladesine / Q000494:pharmacology; D002227:Carbazoles; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004261:DNA Replication; D015237:Dinoprost / Q000096:biosynthesis / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014468:Umbelliferones / Q000494:pharmacology
D044482:Benzeneacetamides; D002227:Carbazoles; D044950:Flavanones; D005419:Flavonoids; D006877:Hydroxamic Acids; D006893:Hydroxyeicosatetraenoic Acids; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D010982:Platelet-Derived Growth Factor; D011758:Pyrroles; D014468:Umbelliferones; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; D016718:Arachidonic Acid; C006680:baicalein; C057416:KT 5720; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D003994:Bucladesine; D015237:Dinoprost; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; C007628:esculetin; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin