Growth of kidney epithelial cells in culture: evidence for autocrine control

The factors that stimulate kidney growth in K+-deficient animals are unknown. Cultures of renal epithelial cells (BSC-1 line) were used to study this phenomenon because their growth is accelerated in medium containing a reduced K+ concentration. We tested the hypothesis that growth induced by low-K+ medium is mediated by factors produced by the cells; i.e., is subject to autocrine control. Low-K+ (3.2 mM) or control (5.4 mM) medium was conditioned by placing it on confluent cultures of BSC-1 cells for 1 h and was then collected. The K+ concentration of the low-K+ conditioned medium was then adjusted to the control value by addition of KCl. This conditioned medium stimulated growth of fresh cultures of cells to the same extent as did unconditioned low-K+ medium. The appearance of growth-promoting activity was maximal at a K+ concentration of 3.2 mM during conditioning of the medium. Low-K+ conditioned medium, corrected to a K+ concentration of 5.4 mM, required 6 h to commit cells to enhanced proliferation. Growth-stimulating activity in low-K+ conditioned medium was antagonized by a purified growth inhibitor produced by the cells. These observations are consistent with the hypothesis that autocrine products with opposite effects on growth can regulate proliferation of renal epithelial cells.