Lowering extracellular Na+ concentration releases autocrine growth factors from renal epithelial cells.

Sodium influx is an important early signal during the onset of mitogenesis in many types of cells. From this observation, one would predict that a decrease in extracellular Na+ concentration might retard cell proliferation. We tested this prediction by exposing sets of cultures of monkey kidney epithelial cells (BSC-1 line) to medium with progressively reduced concentrations of Na+, and we measured the effect on cell multiplication. Unexpectedly, a reduction of the Na+ concentration from 155 mM (control) to 130 mM stimulated proliferation of epithelial cells but not of fibroblasts. Exposure of BSC-1 cells to low Na+ medium for 5 min was sufficient to commit them to accelerated growth. Further study revealed that the cells released two growth factors during this period: anionic proteins with apparent molecular weights of 6200 and 9000 whose properties differ from those of other known growth factors. Thus, a reduction in extracellular Na+ concentration apparently signaled the rapid release of autocrine growth factors that stimulate renal epithelial cell multiplication.