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Renal growth in infancy and childhood--experimental studies of regulatory mechanisms
1Department of Paediatrics, St. Göran's Children's Hospital, Stockholm, Sweden.
Insights
Kidney growth regulation changes with age, influenced by environmental factors and involving cellular proliferation and enlargement. Understanding these developmental changes is key to kidney health.
Area of Science:
- Developmental Biology
- Nephrology
- Cellular Biology
Background:
- Kidney development involves nephrogenesis completion and growth via cell proliferation and enlargement.
- Nephron number is fixed, but cellular growth is sensitive to age-dependent environmental factors.
- Renal growth responses to stimuli like nephrectomy or diet vary significantly with age.
Purpose of the Study:
- To investigate the age-dependent mechanisms regulating kidney growth.
- To understand how cellular proliferation and enlargement are controlled during postnatal development.
- To explore the role of proto-oncogenes and intracellular signaling in kidney growth regulation.
Main Methods:
- Analysis of age-dependent changes in renal growth responses to stimuli.
- Examination of proto-oncogene product expression (growth factor receptors, intracellular signaling components).
- Studies using rat proximal tubule cells in primary culture to assess age-dependent growth regulation.
Main Results:
- Basal proliferative rate of kidney cells is age-dependent.
- Postnatal changes in proliferative response to growth stimulation were observed.
- These changes correlate with altered Na+/H(+)-exchanger response and c-fos proto-oncogene expression.
Conclusions:
- Kidney growth regulation exhibits significant age-dependent plasticity.
- Proto-oncogene expression and intracellular signaling pathways are implicated in these developmental changes.
- Primary cell culture models are valuable for studying kidney growth regulation mechanisms.
Abstract:
During the peri- and early postnatal period, nephrogenesis is completed and kidney growth is accomplished both by cellular proliferation and enlargement. The number of nephrons in a given species is predetermined, whereas cellular growth can be influenced by environmental factors in an age-dependent manner. Unilateral nephrectomy or a high-protein diet stimulates renal growth more in the young than in the adult. Conversely, pyelonephritis inhibits renal growth in infancy but not in adulthood. The relative importance of hyperplasia and hypertrophy for renal growth also changes with renal maturation. The mechanisms behind these developmental changes in regulation of renal growth are largely unknown, but age-dependent changes in the expression of several proto-oncogene products have been demonstrated. These include growth factor receptors as well as components of the intracellular system that transfers the signal from an activated growth factor receptor to the cell nucleus. Studies on rat proximal tubule cells in primary culture might be of great value in expanding our knowledge of growth regulation in the developing kidney. Such studies have already shown that under identical environmental conditions the basal proliferative rate is age dependent, that the proliferative response to growth stimulation changes postnatally, and that this is associated with changes of both the response of the Na+/H(+)-exchanger and the expression of the c-fos proto-oncogene.