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Transforming growth factor-alpha and the ontogeny of epidermal growth factor receptors in rat kidney
P R Goodyer1, J Fata, C G Goodyer
1Department of Pediatrics, McGill University, Montreal Children's Hospital, Quebec, Canada.
Abstract:
Epidermal growth factor exerts potent receptor-mediated mitogenic effects on a variety of target cells in vitro, but its importance in normal organ development is not yet fully understood. We report that the specific high-affinity receptors for EGF/TGF-Alpha increase dramatically in late gestational rat kidney (from 2.3% at 16 days gestation to 6.4% at term) and then fall toward basal adult levels (< 1% binding) during the first week of post-natal life. This post-natal fall-off in EGF binding corresponds temporally to the period when replication of rat kidney DNA begins to slow (4-7 days of post-natal life). EGF mRNA is not detectable in rat kidney by Northern analysis until the second week of post-natal life, but high levels of transforming growth factor-alpha are demonstrable by specific radioimmunoassay in extracts of fetal kidney (52.2 +/- 8.2 pmoles/gram kidney) and amniotic fluid (4.49 +/- 0.75 pmoles/ml). We speculate that induction of EGF-receptors in fetal rat kidney may confer responsiveness to local transforming growth factor-alpha and dictate the rate of hyperplastic renal growth in the perinatal period.
Insights
Epidermal growth factor (EGF) receptors surge in developing rat kidneys, coinciding with rapid growth. Their decline post-birth correlates with slowed DNA replication, suggesting a role in regulating kidney development.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Endocrinology
Background:
- Epidermal growth factor (EGF) is known for its mitogenic effects on various cells in vitro.
- Its precise role in the normal development of organs, particularly the kidney, remains incompletely understood.
Purpose of the Study:
- To investigate the expression and potential role of epidermal growth factor (EGF) receptors and their ligands during rat kidney development.
- To correlate EGF receptor dynamics with kidney growth and DNA replication rates.
Main Methods:
- Quantification of high-affinity EGF/TGF-Alpha receptors using radioligand binding assays at different gestational and post-natal stages.
- Analysis of Epidermal Growth Factor (EGF) mRNA levels via Northern analysis.
- Measurement of transforming growth factor-alpha (TGF-α) levels in fetal kidney and amniotic fluid using radioimmunoassay.
Main Results:
- Specific high-affinity EGF receptors significantly increase in late-gestation rat kidneys, peaking at term, and then decrease post-natally.
- The decrease in EGF receptor binding post-birth temporally aligns with a slowdown in rat kidney DNA replication.
- EGF mRNA is undetectable until the second week post-birth, while high levels of TGF-α are present in fetal kidney and amniotic fluid.
Conclusions:
- EGF receptor induction in the fetal rat kidney may mediate the effects of local TGF-α.
- These interactions are hypothesized to be critical in dictating the rate of hyperplastic renal growth during the perinatal period.