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Lowering extracellular Na+ concentration releases autocrine growth factors from renal epithelial cells
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.
Insights
Lowering extracellular sodium concentration unexpectedly stimulated monkey kidney epithelial cell proliferation by triggering the release of novel autocrine growth factors.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Sodium influx is a known early signal for cell proliferation (mitogenesis).
- A decrease in extracellular sodium concentration was predicted to slow cell growth.
Purpose of the Study:
- To investigate the effect of reduced extracellular sodium on monkey kidney epithelial cell (BSC-1 line) proliferation.
- To understand the underlying mechanisms of sodium's influence on cell growth.
Main Methods:
- Exposing BSC-1 cells to varying concentrations of extracellular sodium.
- Measuring cell multiplication rates.
- Analyzing released factors from cells exposed to low sodium conditions.
Main Results:
- Reduced extracellular sodium (130 mM) unexpectedly stimulated BSC-1 cell proliferation, unlike fibroblasts.
- A brief 5-minute exposure to low sodium medium was sufficient to induce accelerated growth.
- Cells released two novel anionic protein growth factors (MW 6200 and 9000) under low sodium conditions.
Conclusions:
- Extracellular sodium concentration plays a critical role in regulating renal epithelial cell proliferation.
- Reduced sodium triggers the release of specific autocrine growth factors, promoting cell multiplication.
- This finding challenges the initial prediction and reveals a novel mechanism of cell growth regulation.