Nephrol Dial Transplant (2002) 17: 2-4
© 2002 European Renal Association-European Dialysis and Transplant Association
Signal Transduction in Renal Development
Cell turnover in normal and abnormal kidney development
Nephro-Urology Unit, Institute of Child Health, London WC1N 1EH, UK
Abstract
As metanephric mesenchyme converts into nephrons, the first step is aggregation into a ‘condensate’. Precursors inside this structure are proliferative and have a low rate of apoptosis, accompanied by expression of PAX-2 and BCL-2 survival molecules; conversely, cells at the borders of the structure have a high rate of apoptosis, probably a normal mechanism to regulate the number of cells in each nephron. Ureteric bud/collecting duct survival and mitosis may be determined partly by renal mesenchymal secreted molecules such as hepatocyte growth factor (HGF) and glial cell line-derived neurotrophic factor. Human kidney malformations often occur with lower urinary tract obstruction, e.g. cystic dysplastic kidneys caused by urethral valves. Deregulation of cell turnover occurs in these organs, with enhanced proliferation in cystic epithelium, accompanied by PAX-2, BCL-2 and HGF receptor expression, and apoptosis in surrounding mesenchyme, which transdifferentiates under the influence of transforming growth factor-ß1 into smooth muscle instead of forming nephrons. Similar abnormalities of cell turnover and gene expression can be generated by experimental fetal urinary flow impairment. Finally, renal mesenchmal apoptosis, associated with renal hypoplasia, can be induced experimentally by maternal low protein diet.
Keywords: apoptosis; epithelium; malformation; mesenchyme; proliferation
Notes
Correspondence and offprint requests to: Professor Adrian S. Woolf, Nephro-Urology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
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