Key Points
- To investigate whether prorenin and renin stimulate ERK 1/2 activation via the (pro)renin receptor in human monocytes and whether this pathway is blocked by aliskiren or handle-region peptide.
- Measured (pro)renin receptor mRNA and protein expression in primary human monocytes and the U937 monocyte cell line.
- Stimulated U937 monocytes with human renin and prorenin in the presence of angiotensin II type 1 and 2 receptor blockers, EGFR inhibitors, or a MEK 1/2 inhibitor.
- Assessed receptor binding and pathway inhibition using radioligand binding assays, flow cytometry, the renin inhibitor aliskiren, and handle-region peptide.
- Both renin and prorenin induced sustained ERK 1/2 phosphorylation in U937 cells independently of angiotensin II receptors and EGFR, which was suppressed by MEK 1/2 inhibition.
- Neither aliskiren nor the handle-region peptide blocked the binding of (125)I-renin or (125)I-prorenin to the (pro)renin receptor.
- Aliskiren and the handle-region peptide failed to inhibit renin- or prorenin-stimulated ERK 1/2 phosphorylation and kinase activity.
Structured PICO
PPopulationIsolated human monocytes and U937 monocytes
IInterventionAliskiren or handle-region peptide (HRP) in the presence of human prorenin and renin
OOutcomeExtracellular signal-regulated kinase (ERK) 1/2 activation/phosphorylation and binding to (pro)renin receptor [(P)RR]surrogate
In human monocytes, prorenin and renin induce ERK 1/2 activation independently of angiotensin II, and this signaling is not blocked by the direct renin inhibitor aliskiren or the handle-region peptide.