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Expression of transforming growth factor-alpha and epidermal growth factor receptor in human fetal kidneys
P R Goodyer1, J Fata, L Mulligan
1Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
Abstract:
Beginning at the fifth week of fetal life, successive generations of individual nephrons are induced by contact between metanephric mesenchyme and ureteric bud. Following phenotypic transformation, cells of each primitive renal vesicle undergo a phase of rapid cell division. In order to identify genes which might regulate nephron development in man, we screened adult and fetal kidney RNA for expression of a panel of growth-related genes. Among the genes which were expressed at higher levels in fetal kidney was the epidermal growth factor (EGF) receptor. There is controversy as to the most likely physiologic EGF receptor ligand in fetal kidney; we were able to identify a transcript for transforming growth factor-alpha (TGF-alpha) but not EGF on Northern blots of fetal kidney RNA. Since the abundance of TGF-alpha mRNA is low, we confirmed its presence by polymerase chain reaction amplification. Using specific radioimmunoassays, we also provide direct evidence for TGF-alpha but not EGF peptide in extracts of fetal kidney and mid-gestational amniotic fluid. We suggest that TGF-alpha/EGF receptor interactions may serve an important function in development of human fetal kidney.
Insights
Transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor (EGF) receptor are key in human fetal kidney development. This study identifies TGF-alpha as the likely ligand, crucial for regulating nephron formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Nephrology
Background:
- Nephron development in humans begins around the fifth week of gestation.
- This process involves interactions between metanephric mesenchyme and ureteric bud, leading to primitive renal vesicle formation and rapid cell division.
Purpose of the Study:
- To identify genes regulating human nephron development.
- To investigate the role of growth-related genes, specifically the epidermal growth factor (EGF) receptor and its ligands, in the fetal kidney.
Main Methods:
- Screening of adult and fetal kidney RNA for growth-related gene expression.
- Northern blotting to detect specific RNA transcripts, including transforming growth factor-alpha (TGF-alpha) and EGF.
- Polymerase chain reaction (PCR) amplification to confirm low-abundance mRNA.
- Radioimmunoassays to detect peptide presence in tissue extracts and amniotic fluid.
Main Results:
- The epidermal growth factor (EGF) receptor was expressed at higher levels in fetal kidney RNA.
- A transcript for TGF-alpha was identified in fetal kidney RNA, but not EGF.
- Direct evidence of TGF-alpha peptide, but not EGF peptide, was found in fetal kidney extracts and amniotic fluid.
Conclusions:
- TGF-alpha is likely the primary physiological ligand for the EGF receptor in the developing human fetal kidney.
- TGF-alpha/EGF receptor signaling pathways may play a significant role in human fetal kidney development and nephrogenesis.