EXPRESSION OF THE CYCLIN KINASE INHIBITOR, P27(KIP1), IN DEVELOPING AND MATURE HUMAN KIDNEY

It has been shown that glomerular visceral epithelial cells (VEC) prol iferate during glumerulogenesis, but differentiated VEC of the fetal k idney do not. It is also recognized that the proliferative capacity of the VEC In mature kidneys is very limited, and, according to some inv estigators, mag-be completely absent. The basis for this remains unkno wn. Cell proliferation is controlled by cell cycle-related proteins, o f which one class, the cyclin kinase inhibitors (CKI), cause cell cycl e arrest and inhibit proliferation, A role for CKI In kidney developme nt is not known. Accordingly, we examined the expression of the (SKI p 27(kip1) (p27) in developing and mature human kidney tissue. Concomita nt expression of markers of cell proliferation, Ki67-related antigen ( Ki-67) and proliferating cell nuclear antigen (PCNA), also were examin ed in fetal and mature human kidney tissue bq immunocytochemical techn iques. In developing kidney, Ki-67 and PCNA expression are most pronou nced in the nephrogenic tent: where expression correlates inversely wi th increasing glomerular maturation. In well-differentiated glomeruli, Ki-67 and PCNA expression is present in some parietal epithelial cell s but is absent in the VEC. In contrast, p27 staining exhibits a rever se gradient of expression. p27 is absent in the proliferating tissue e xhibiting the earliest stages of differentiation, whereas expression i s widespread in the differentiated epithelial cells of more mature glo meruli, in which detectable cell proliferation has ceased. Expression of p27 was not identified in fetal mesangial or glomerular endothelial cells. In the mature human kidney, the pattern of p27 expression iden tified in differentiated fetal glomeruli persists and appears to be co nstitutive and specific fur glomerular VEC. This pattern of p27 expres sion in terminally differentiated VEC may explain their limited prolif erative capacity in response to injury. This is the first demonstratio n of a potential role for p27 in human renal development.