In vitro characterization of renal reabsorption and secretion of folate using primary cultures of human kidney cells

Abstract

Proximal tubule cells in the kidney play an important role in the homeostasis of folate. Mechanistic studies on folate reabsorption and secretion across the proximal tubular epithelium have been limited. The present studies were aimed at assessing the suitability of human proximal tubule (HPT) cells cultured on membrane inserts as an in vitro model of renal folate processing by examining aspects of folate transport from the apical to basolateral (A-B, reabsorptive) and from the basolateral to apical (B-A, secretory) directions. The data demonstrate that apical membrane binding and cellular uptake of folate in HPT cells were mediated via specific high affinity mechanisms. Apical binding and cellular uptake of folate occurred in a greater proportion from the A-B direction than from the B-A direction, suggesting that folate reabsorption may be the dominant process in HPT cells. However, cellular uptake did occur readily from the B-A direction, in amounts greater than could be explained by leakage through the cell barrier to the apical media, followed by uptake from the A-B direction. These data suggest the presence of specific folate secretory processes in HPT cells. Folate was transferred across the cell layer into the opposite media compartments from both directions, but apparently by nonspecific processes. The present studies suggest that primary cultures of HPT cells grown on microporous membrane inserts may serve as a valuable in vitro model to study the bidirectional transport of folate by kidney cells.