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

Dominko Carev1, Dragan Krnić, Marijan Saraga

  • 1Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, PAK, KB Split, Spincieva 1, 21000, Split, Croatia.

Pediatric Nephrology (Berlin, Germany)
|March 29, 2006
PubMed

Insights

Investigating human kidney development, this study reveals that cell proliferation and apoptosis are crucial for mesonephros and metanephros formation. Protein expression patterns, including Ki-67, bcl-2, caspase-3, and p53, highlight their roles in regulating kidney development and survival.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Human Embryology

Background:

  • The development of human kidneys, including the mesonephros and metanephros, involves complex processes of cell proliferation, differentiation, and programmed cell death.
  • Understanding the molecular mechanisms governing these processes is crucial for identifying potential causes of congenital kidney abnormalities.

Purpose of the Study:

  • To investigate the spatiotemporal expression patterns of key proteins involved in cell proliferation (Ki-67), anti-apoptosis (bcl-2), and apoptosis (caspase-3, p53) during early human kidney development (5-9 weeks post-conception).
  • To elucidate the roles of these proteins in the morphogenesis of the mesonephros and metanephros.

Main Methods:

  • Immunohistochemistry was used to detect the expression of Ki-67, bcl-2, caspase-3, and p53 proteins in human mesonephros and metanephros tissues from 5-9 week-old conceptuses.
  • The terminal deoxynucleotidyl transferase (TdT) nick-end labelling (TUNEL) method was employed to detect apoptotic cells.

Main Results:

  • In the mesonephros (5-7 weeks), Ki-67, caspase-3, and TUNEL positivity indicated significant cell proliferation and apoptosis. p53 and bcl-2 appeared later (from 7 weeks), potentially regulating regression and survival.
  • In the metanephros (5-7 weeks), Ki-67 was widespread, supporting ureteric bud branching and nephron formation. Bcl-2, caspase-3, and TUNEL were localized to the mesenchyme and nephrons, suggesting bcl-2 protects nephrons and caspase-3 mediates mesenchymal cell death.
  • From 7-9 weeks, p53 expression in the metanephros suggested a role in collecting system morphogenesis.

Conclusions:

  • The expression of Ki-67, bcl-2, caspase-3, and p53 proteins follows specific spatial and temporal patterns during human kidney development.
  • These proteins play critical roles in regulating cell proliferation, apoptosis, and survival, thereby influencing the proper formation and morphogenesis of both the mesonephros and metanephros.
  • Aberrations in these expression patterns during early development may lead to severe kidney malformations and functional deficits in early childhood.

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