Further studies on the characterization of a renotropic activity detected in uninephrectomized rat plasma.

Using chromatographic techniques, we have purified a peptide responsible, at least in part, for the renotropic activity detected in 24-hour uninephrectomized adult rat plasma. The most purified material behaved as a single component when analyzed by reversed-phase HPLC. The purified factor stimulates DNA synthesis in isolated rat proximal tubules and proximal tubular cell (LLC-PK1) cultures. This effect was abolished by pretreatment with protease K, with an intracellular calcium chelator or with indomethacin. This factor was also mitogenic for rat mesangial cells. In contrast, neither Madin-Darby canine kidney cells nor rat liver cells responded to the growth factor. Using the same purification procedure, a bioactive factor with an amino acid composition almost identical to that of this renotropic peptide was isolated from sham-operated or normal rat plasma. However, only uninephrectomized plasma after gel filtration showed renotropic activity, which was inhibited by the corresponding chromatographic fraction from sham-operated plasma. Our findings suggest that a change in the concentration of a circulating inhibitor(s) appears to account for the differences in the activity of sham-operated or control plasma and uninephrectomized plasma on the growth of renal cells.