BACKGROUND

Prostaglandin E2 (PGE) regulates renin expression in renal juxtaglomerular cells. PGE acts through E-prostanoid (EP) receptors in the renal collecting duct (CD) to regulate sodium and water balance. CD cells express EP1 and EP4, which are linked to protein kinase C (PKC) and PKA downstream pathways, respectively. Previous studies showed that the presence of renin in the CD, and that of PKC and PKA pathways, activate its expression. The (pro)renin receptor (PRR) is also expressed in CD cells, and its activation enhances cyclooxygenase-2 (COX-2) through extracellular signal-regulated kinase (ERK). We hypothesized that PGE stimulates prorenin and renin synthesis leading to subsequent activation of PRR and upregulation of COX-2.

METHODS

We used a mouse M-1 CD cell line that expresses EP1, EP3 and EP4 but not EP2.

RESULTS

PGE (10M) treatment increased prorenin and renin protein levels at 4 and 8 hours. No differences were found at 12-hour after PGE treatment. Phospho-ERK was significantly augmented after 12 hours. COX-2 expression was decreased after 4 hours of PGE treatment, but increased after 12 hours. Interestingly, the full-length form of the PRR was upregulated only at 12 hours. PGE-mediated phospho-ERK and COX-2 upregulation was suppressed by PRR silencing.

CONCLUSIONS

Our results suggest that PGE induces biphasic regulation of COX-2 through renin-dependent PRR activation via EP1 and EP4 receptors. PRR-mediated increases in COX-2 expression may enhance PGE synthesis in CD cells serving as a buffer mechanism in conditions of activated renin-angiotensin system.