Involvement of prostaglandin E-2 in clearance of aggregated protein via protein kinase A in glomeruli

Recently we immunohistochemically demonstrated that prostaglandin E-2 (PGE( 2)) promoted the clearance of aggregated bovine serum albumin (a-BSA) depos ited in glomeruli. Herein, we investigated the role of PGE(2) and its signa l transduction in the disposal of macromolecules in glomeruli. EP2 and EP4 receptor mRNA was detected in glomeruli by RT-PCR analysis. A-BSA was injec ted twice into mice. Glomeruli were then isolated and incubated. B-BSA grad ually disappeared from isolated glomeruli. PGE(2) increased the intracellul ar cyclic AMP and decreased a-BSA level in glomeruli. Additionally, 8-bromo -cyclic AMP evoked a loss of a-BSA in isolated glomeruli. The effect of 8-b romo-cyclic AMP on the clearance of a-BSA was abolished by KT 5720 in glome ruli. PGE(2) and 8-bromo-cyclic AMP also prompted disposal of a-BSA in cult ured mesangial cells. These findings indicate that PGE(2) positively regula tes the removal of macromolecules via cyclic AMP and protein kinase A in gl omeruli, and they provide insight into how to prevent the development of gl omerulonephritis and glomerulosclerosis.