Abstract

The PRR binds equally to renin and its precursor prorenin, leading to a similar intracellular signaling independent of angiotensin II. Recently, it was reported that PRR is a component of the Wnt signalling pathway working as an adaptor between Wnt receptors and the vacuolar H+-ATPase complex. The expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals; however its role in renal damage is still unclear. In this study we investigated whether the PRR activation induces the expression of fibronectin and collagen I via the β-catenin pathway in mouse collecting duct cell line M-1. Human recombinant prorenin (hrPR) treatment by 16 h in M-1 cells increased the mRNA and protein levels of fibronectin, Collagen I, and the β-catenin target genes, cyclin D1 and c-myc. Inhibition of β-catenin degradation with pyrvinium pamoate (pyr, 10-9 M) does not prevented the hrPR-induced expression of all these genes. However, when the cells were transfected with a siRNA targeting the PRR, the hrPR-induced expression of fibronectin, collagen, cyclin D1 and c-myc it was prevented. In addition, hrPR treatment did not change the stationary protein level of β-catenin or phosphorylation of GSK-3β until 24h, but the level of pERK1/2 displayed a time-dependent increase. The results suggest that in M-1 collecting duct cells, activation of the PRR by prorenin promote fibrotic genes expression independent of β-catenin signaling pathway.