Role of mitotic, pro-apoptotic and anti-apoptotic factors in human kidney development

Abstract

The expression pattern of mitotic Ki-67 and anti-apoptotic bcl-2 proteins, as well as apoptotic caspase-3 and p53 proteins, were investigated in the human mesonephros and metanephros of 5-9 week-old human conceptuses. Apoptotic cells were additionally detected using the terminal deoxynucleotidyl transferase (TdT) nick-end labelling (TUNEL) method. Between the 5th and 7th developmental weeks Ki-67, caspase-3 and TUNEL-positive cells characterized all mesonephric structures, indicating importance of cell proliferation in the growth of the mesonephros and role of apoptosis in nephrogenesis. From the 7th week on, p53 and bcl-2 positive cells appeared in the mesonephros as well. Regressive changes in the mesonephros could be regulated by activation of p53, while bcl-2 could contribute to selective survival of some tubules giving rise to adult structures. In the early human metanephros (5-7 weeks), Ki-67 positive cells characterized all metanephric structures, indicating a role of cell proliferation in branching of the ureteric bud and in nephron formation. During the same period bcl-2, caspase-3 and TUNEL-positive cells were found only in the metanephric mesenchyme and nephrons. Bcl-2 protein probably protected nephrons from apoptosis, while caspase-3 protein controlled cell death in the mesenchyme. At later stages (7-9-weeks), appearance of p53-expressing cells could participate in further morphogenesis of the metanephric collecting system. The factors investigated had a spatially and temporally restricted pattern of appearance in developing kidneys. Changes in that pattern might lead to serious disturbances of kidney formation and function in early childhood.

Kidney and urinary tract development: an apoptotic balancing act

“…1b) [47]. Interestingly, these studies also suggest that p53 may be the upstream inducer of death [47]; however, in transgenic mice, no defects in mesonephric tubule regression or metanephric kidney apoptosis have been noted [48]. Finally, clearance of the apoptotic bodies resulting from disintegration of the mesonephros appears to be mediated by hemopoietically derived specialist macrophages which aggregate within and adjacent to mesonephric tubules [49].…”

“…Gene expression studies in human kidney development indicate that caspase-3-mediated apoptosis is associated with regression of these transient kidneys (Fig. 1b) [47]. Interestingly, these studies also suggest that p53 may be the upstream inducer of death [47]; however, in transgenic mice, no defects in mesonephric tubule regression or metanephric kidney apoptosis have been noted [48].…”

“…During normal ureteric bud invasion and branching in the mouse, apoptotic bodies are observed in both the epithelial and mesenchymal compartments, although the highest proportion of cell death occurs in the metanephric mesenchyme (Fig. 1b) [21,44,47]. Most apoptosis in the mesenchyme occurs close to, but not within differentiated nephron epithelia, presumably as it is preserved by pro-survival signals, although as time progresses more apoptotic bodies are seen within the podocyte region [21,44,47].…”

Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease

“…Enhanced apoptosis accompanies increased cell proliferation in polycystic kidneys (84,85), as occurs during renal development (86)(87)(88) and tubular regeneration following AKI (89,90), where it is important for morphogenesis. An imbalance favoring proliferation over apoptosis contributes to the development of cysts, epithelial hyperplasia, and microscopic adenomas in PKD (91,92), but enhanced apoptosis may be sufficient to reduce the risk for development of renal cell carcinoma (93).…”

Expression of Cyt-c-Mediated Mitochondrial Apoptosis-Related Proteins in Rat Renal Proximal Tubules during Development

“…UBs form in the collecting tubules, renal calyces and renal pelvis. These processes are strictly controlled via proliferation and cell death to ensure that they occur at the right time and in the right sequence to build and maintain the various cell populations present in the different structures [3,4,5,6]. …”