Effects of endogenously produced arachidonic acid metabolites on rat mesangial cell proliferation

Abstract

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) E 2 and F 2α 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 PGE 2, but not with PGF 2α. To test whether the mechanism by which PGE 2 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 PGE 2 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.