Replication of segment-specific and intercalated cells in the mouse renal collecting system

Abstract

The renal collecting system (CS) is composed of segment-specific (SS) and intercalated (IC) cells. The latter comprise at least two subtypes (type A and non-type A IC). The origin and maintenance of cellular heterogeneity in the CS is unclear. Among other hypotheses, it was proposed that one subtype of IC cells represents a stem cell population from which all cell types in the CS may arise. In the present study, we tested this stem cell hypothesis for the adult kidney by assessing DNA synthesis as a marker for cell replication. SS and IC cells were identified by their characteristic expressions of sodium- (epithelial sodium channel, Na-K-ATPase), water- (aquaporin-2) and acid/base- (H+ -ATPase, anion exchanger AE1) transporting proteins. Immunostaining for bromodeoxyuridine (BrdU) and for the proliferating cell nuclear antigen (PCNA) was used to reveal DNA synthesis in CS epithelium. BrdU- and PCNA-immunostaining as well as mitotic figures were seen in all subtypes of CS cells. Dividing cells retained the cell-type specific expression of marker molecules. Treatment of mice with bumetanide combined with a high oral salt intake, which increases the tubular salt load in the CS, profoundly increased the DNA-synthesis rate in SS and non-type A IC cells, but reduced it in type A IC cells. Thus, our data show that DNA synthesis and cell replication occur in each cell lineage of the CS and in differentiated cells. The replication rate in each cell type can be differently modulated by functional stimulation. Independent proliferation of each cell lineage might contribute to maintain the cellular heterogeneity of the CS of the adult kidney and may also add to the adaptation of the CS to altered functional requirements.