The effect of the (pro)renin receptor on the activation of extracellular signal-regulated kinases 1 and 2 on human renal mesangial cells

Abstract

Objectives: To investigate whether human prorenin can provoke the (pro)renin receptor [(P)RR] leading to the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and whether the putative (pro)renin receptor blocker “handle-region” peptide (HRP) inhibits this pathway in cultured human renal mesangial cells (HRMCs). Methods: HRMCs were cultured in vitro. HRMCs were pretreated with the AT1 blocker olmesartan and AT2 blocker PD123319 blocker for 30 min, then HRMCs were stimulated by prorenin, PD98059 inhibitor of the phosphorylation of ERK1/2 and HRP respectively. Western blot was used to test the concentration of p-ERK1/2. The concentration of transfer growth factor-β1 (TGF-β1) was measured by the ELASA method. The mRNA of TGFβ1 was measured by the RT-PCR method. Results: We found that recombinant human prorenin induced the activation of (P)RR in cultured HRMCs, and in turn, increased the phosphorylated ERK1/2. Recombinant humanprorenin induced a rapid phosphorylation of ERK1/2 and pREK1/2 which increased in a timeand dose-dependent way, and the prorenin levels of TGF-β1 increased significantly. We also found that an ERK inhibitor PD98059 significantly decreased the phosphorylated ERK1/2 and then down regulated the TGF-β1. The putative blocker HRP of (P)RR which consisted of the handle-region decoy peptide of prorenin inhibits neither the phosphorylation of ERK1/2 nor the increase of TGFβ1. Conclusion: Prorenin induced a long-lasting ERK1/2 phosphorylation in a timeand concentration-dependent manner in HRMCs. The signal transduction is different from that which is provoked by Ang II. TGF-β1 increased obviously accompanied by the ERK1/2 phosphorylation. PD98059 decreased the production of TGF-β1 induced by (P)RR. HRP affects neither the signaling in HRMCs nor the TGF-β1.