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

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Abstract
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.