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GROWTH, DIFFERENTIATION, AND APOPTOSIS

Proliferation capacity of the renal proximal tubule involves the bulk of differentiated epithelial cells

¹Institute of Anatomy, University of Zurich; and ²Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland

Submitted 1 June 2007 ; accepted in final form 19 September 2007

We investigated the proliferative capacity of renal proximal tubular cells in healthy rats. Previously, we observed that tubular cells originate from differentiated cells. We now found 1) by application of bromo-deoxyuridine (BrdU) for 14 days and costaining for BrdU, and the G₁-phase marker cyclin D1 that the bulk of cells in the S3 segment of juvenile rats were involved in proliferation; 2) that although the proliferation rate was about 10-fold higher in juvenile rats compared with adult rats, roughly 40% of S3 cells were in G₁ in both groups; 3) that after a strong mitotic stimulus (lead acetate), proliferation was similar in juveniles and adults; 4) that there was a high incidence of cyclin D1-positive cells also in the healthy human kidney; and 5) by labeling dividing cells with BrdU for 2 days before the application of lead acetate and subsequent costaining for BrdU and cell cycle markers, that, although a strong mitotic stimulus does not abolish the period of quiescence following division, it shortens it markedly. Thus the capacity of the proximal tubule to rapidly recruit cells into division relies on a large reserve pool of cells in G₁ and on the shortening of the obligatory period of quiescence that follows division.

kidney; cyclin D1; bromodeoxyuridine; stem cells; regeneration

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