COMPARISON OF ANTIPROLIFERATIVE EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDEAND TRANSFORMING GROWTH-FACTOR-BETA ON RABBIT KIDNEY PROXIMAL TUBULE CELLS

The effects of atrial natriuretic peptide (ANP) and transforming growt h factor beta (TGF beta) on cell proliferation were investigated in ra bbit kidney proximal tubule cells. At 48h, each agonist inhibited cell growth dose dependently. Moreover, the antiproliferative effect of bo th factors together was greater than that of each factor alone. Howeve r, coincubation of a high concentration (100 nM) of ANP and epidermal growth factor (EGF) was found to induce cell hypertrophy. This hypertr ophic effect induced by ANP in the presence of EGF was mimicked by 8-B rcGMP but not by various cAMP analogues, at 100 mu M, and was independ ent of the tyrosine kinase inhibitor genistein (10 mu M). However, it was inhibited by 100 pM TGF beta. These in vitro results suggest that the antiproliferative effects of ANP and TGF beta may be part of a mec hanism to modulate the hyperplastic effect of EGF in the renal proxima l tubule during compensatory kidney growth.