title: Proliferation of acid-secretory cells in the kidney during adaptive remodelling of the collecting duct.
abstract: The renal collecting duct adapts to changes in acid-base metabolism by remodelling and altering the relative number of acid or alkali secreting cells, a phenomenon termed plasticity. Acid secretory A intercalated cells (A-IC) express apical H(+)-ATPases and basolateral bicarbonate exchanger AE1 whereas bicarbonate secretory B intercalated cells (B-IC) express basolateral (and apical) H(+)-ATPases and the apical bicarbonate exchanger pendrin. Intercalated cells were thought to be terminally differentiated and unable to proliferate. However, a recent report in mouse kidney suggested that intercalated cells may proliferate and that this process is in part dependent on GDF-15. Here we extend these observations to rat kidney and provide a detailed analysis of regional differences and demonstrate that differentiated A-IC proliferate massively during adaptation to systemic acidosis. We used markers of proliferation (PCNA, Ki67, BrdU incorporation) and cell-specific markers for A-IC (AE1) and B-IC (pendrin). Induction of remodelling in rats with metabolic acidosis (with NH(4)Cl for 12 hrs, 4 and 7 days) or treatment with acetazolamide for 10 days resulted in a larger fraction of AE1 positive cells in the cortical collecting duct. A large number of AE1 expressing A-IC was labelled with proliferative markers in the cortical and outer medullary collecting duct whereas no labeling was found in B-IC. In addition, chronic acidosis also increased the rate of proliferation of principal collecting duct cells. The fact that both NH(4)Cl as well as acetazolamide stimulated proliferation suggests that systemic but not urinary pH triggers this response. Thus, during chronic acidosis proliferation of AE1 containing acid-secretory cells occurs and may contribute to the remodelling of the collecting duct or replace A-IC due to a shortened life span under these conditions.
authors: Institute of Anatomy, University of Zurich, Zurich, Switzerland.
authors: Desa
authors: D
authors: Welsh-Bacic
authors: Marta
authors: M
authors: Nowik
authors: Brigitte
authors: B
authors: Kaissling
authors: Carsten A
authors: CA
authors: Wagner
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism / Q000502:physiology*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018809:Proliferating Cell Nuclear Antigen