Physiological changes in extracellular sodium directly control human proximal tubule growth and transport.

TLDR: It is confirmed that physiological increases in extracellular Na+ concentration directly stimulate human proximal tubule growth and Na+ transport and does not appear to be mediated by altered PTC secretion of, or responsiveness to, cytokines known to affect tubulegrowth and transport.

Abstract: In order to examine the nature and potential mechanisms of action of extracellular sodium on human proximal tubule growth and transport, quiescent primary cultures of human proximal tubule cells (PTC) were incubated for 24 h in serum-free, growth-factor-free culture media containing low (130 mmol/l), control (140 mmol/l) or high (150 mmol/l) Na+. Compared to control conditions, cells exposed to a high Na+ concentration demonstrated stimulated thymidine incorporation (121.8 ± 7.6%, P 0.1). Substitution of choline chloride for NaCl did not replicate these effects. Conversely, cells incubated in low-Na+ media showed reduced thymidine incorporation (77.2 ± 4.4%, P 0.1) and transforming growth factor-β1 (1.76 ± 0.32, 1.73 ± 0.33 and 1.45 ± 0.28 ng/mg protein, P > 0.1), and did not exhibit autocrine growth factor activity on separate PTC following adjustment of Na+ concentrations to 140 mmol/l by dialysis. Similarly, low-Na+, control or high-Na+ media did not modify the mitogenic responsiveness of PTC to insulin-like growth factor-I (IGF-I) or alter the affinity or number of PTC IGF-I binding sites. The results confirm that physiological increases in extracellular Na+ concentration directly stimulate human proximal tubule growth and Na+ transport. Such stimulation does not appear to be mediated by altered PTC secretion of, or responsiveness to, cytokines known to affect tubule growth and transport.