Key result
Rat recombinant prorenin (100 nmol/L) upregulated COX-2 expression in rat renal inner medullary cells independently of AT1R blockade via extracellular regulated kinases 1/2.
The study demonstrates that the (pro)renin receptor can upregulate COX-2 expression independently of the AT1 receptor via ERK 1/2 pathways in rat renal inner medullary cells.
Hypothesis-generating for (pro)renin receptor signaling in renal cells; leaves open any clinical relevance in hypertension.
During renin-angiotensin system activation, cyclooxygenase-2 (COX-2)-derived prostaglandins attenuate the pressor and antinatriuretic effects of angiotensin II (AngII) in the renal medulla. The (pro)renin receptor (PRR) is abundantly expressed in the collecting ducts (CD) and its expression is augmented by AngII. PRR overexpression upregulates COX-2 via mitogen-activated kinases/extracellular regulated kinases 1/2 in renal tissues; however, it is not clear whether this effect occurs independently or in concert with AngII type 1 receptor (AT1R) activation. We hypothesized that PRR activation stimulates COX-2 expression independently of AT(1)R in primary cultures of rat renal inner medullary cells. The use of different cell-specific immunomarkers (aquaporin-2 for principal cells, anion exchanger type 1 for intercalated type-A cells, and tenascin C for interstitial cells) and costaining for AT(1)R, COX-2, and PRR revealed that PRR and COX-2 were colocalized in intercalated and interstitial cells whereas principal cells did not express PRR or COX-2. In normal rat kidney sections, PRR and COX-2 were colocalized in intercalated and interstitial cells. In rat renal inner medullary cultured cells, treatment with AngII (100 nmol/L) increased COX-2 expression via AT(1)R. In addition, AngII and rat recombinant prorenin (100 nmol/L) treatments increased extracellular regulated kinases 1/2 phosphorylation, independently. Importantly, rat recombinant prorenin upregulated COX-2 expression in the presence of AT(1)R blockade. Inhibition of mitogen-activated kinases/extracellular regulated kinases 1/2 suppressed COX-2 upregulation mediated by either AngII or rat recombinant prorenin. Furthermore, PRR knockdown using PRR-short hairpin RNA blunted the rat recombinant prorenin-mediated upregulation of COX-2. These results indicate that COX-2 expression is upregulated by activation of either PRR or AT(1)R via mitogen-activated kinases/extracellular regulated kinases 1/2 in rat renal inner medullary cells.
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González et al. (2012) studied this question. Rat recombinant prorenin and Angiotensin II was evaluated on COX-2 expression. Rat recombinant prorenin (100 nmol/L) upregulated COX-2 expression in rat renal inner medullary cells independently of AT1R blockade via extracellular regulated kinases 1/2.
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