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Developmental regulation of CFTR expression during human nephrogenesis
O Devuyst1, C R Burrow, E M Schwiebert
1Department of Medicine, Johns Hopkins University, Medical School, Baltimore, Maryland 21205, USA.
The American Journal of Physiology
|September 1, 1996
Summary
Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in developing human kidneys, with distinct patterns in tubules and a novel splice variant identified. This reveals complex CFTR regulation during kidney development.
Area of Science:
- Nephrology
- Developmental Biology
- Molecular Biology
Background:
- Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA and protein are known to be present in adult human kidney tubules.
- The expression pattern of CFTR during human kidney development (nephrogenesis) has not been previously characterized.
Purpose of the Study:
- To investigate the spatiotemporal expression of CFTR during human kidney development.
- To identify potential CFTR splice variants expressed in the developing human kidney.
Main Methods:
- Immunohistochemistry was used to examine CFTR protein localization in fetal human kidneys at various gestational ages (12-24 weeks).
- Western blot analysis was performed on fetal kidney extracts to detect CFTR protein size and expression levels.
- Multiple antibodies targeting different regions of CFTR were employed.
Main Results:
- CFTR was detected in the apical membrane of ureteric bud epithelial cells by 12 weeks of gestation.
- By 15 weeks, CFTR expression extended to the cytoplasm of proximal tubules and loops of Henle, persisting throughout development.
- A 165-kDa full-length CFTR protein and a 75-kDa splice variant were identified, with the latter showing developmental regulation.
Conclusions:
- CFTR expression is complex and dynamically regulated during human nephrogenesis.
- The identification of a novel, developmentally regulated CFTR splice variant in the human kidney warrants further investigation into its functional significance.