Inhibition of renin/prorenin receptor attenuated mesangial cell proliferation and reduced associated fibrotic factor release

Abstract

The present study was designed to investigate the physiological roles of renin/prorenin receptor in cultured rat mesangial cells. The presence of renin/prorenin receptor in mesangial cells was determined by immunofluorescence staining, real-time quantitative reverse transcriptase-polymerase chain reaction (real-time PCR) and Western blotting assay. The expression of renin/prorenin receptors was identified in both rat renal slices and cultured mesangial cells. Meanwhile, the cultured mesangial cells were demonstrated synthesizing and secreting (Pro)renin as well. Knockdown of renin/prorenin receptor expression was performed by small interfering RNA (siRNA) transfection. Either knockdown or blockade of renin/prorenin receptor by handle region peptide (HRP) reduced mesangial cell proliferation. In the meantime, release of type IV collagen, phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and mRNA level of transforming growth factor-β1 (TGF-β1) were decreased. On the other hand, both the production and activity of matrix metalloproteinase-2, a key enzyme to degrade type IV collagen, was increased. The present results indicated that renin/prorenin receptor played a regulatory role in mesangial cells proliferation and extracellular matrix accumulation. Blockade of renin/prorenin receptors may postpone over extracellular accumulation, which occurs in some pathological situations, via suppressed both mesangial cell proliferation and fibrotic factor release.