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Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney
- Source :
- Journal of the American Society of Nephrology. 26:149-159
- Publication Year :
- 2015
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2015.
-
Abstract
- A disintegrin and metalloproteinase domain 10 (Adam10), a member of the ADAM family of cell membrane-anchored proteins, has been linked to the regulation of the Notch, EGF, E-cadherin, and other signaling pathways. However, it is unclear what role Adam10 has in the kidney in vivo. In this study, we showed that Adam10 deficiency in ureteric bud (UB) derivatives leads to a decrease in urinary concentrating ability, polyuria, and hydronephrosis in mice. Furthermore, Adam10 deficiency led to a reduction in the percentage of aquaporin 2 (Aqp2)(+) principal cells (PCs) in the collecting ducts that was accompanied by a proportional increase in the percentage of intercalated cells (ICs). This increase was more prominent in type A ICs than in type B ICs. Foxi1, a transcription factor important for the differentiation of ICs, was upregulated in the Adam10 mutants. The observed reduction of Notch activity in Adam10 mutant collecting duct epithelium and the similar reduction of PC/IC ratios in the collecting ducts in mice deficient for mindbomb E3 ubiquitin protein ligase 1, a key regulator of the Notch and Wnt/receptor-like tyrosine kinase signaling pathways, suggest that Adam10 regulates cell fate determination through the activation of Notch signaling, probably through the regulation of Foxi1 expression. However, phenotypic differences between the Adam10 mutants, the Mib1 mutants, and the Foxi1 mutants suggest that the functions of Adam10 in determining the fate of collecting duct cells are more complex than those of a simple upstream factor in a linear pathway involving Notch and Foxi1.
- Subjects :
- medicine.medical_specialty
Notch signaling pathway
Apoptosis
Mice, Transgenic
Hydronephrosis
Cell fate determination
Kidney
Ligands
ADAM10 Protein
Mice
Internal medicine
medicine
Animals
Kidney Tubules, Collecting
Wnt Signaling Pathway
Transcription factor
Cell Proliferation
Aquaporin 2
Receptors, Notch
biology
Polyuria
Stem Cells
Wnt signaling pathway
Membrane Proteins
Epithelial Cells
Forkhead Transcription Factors
General Medicine
Cadherins
Up-Regulation
Ubiquitin ligase
Cell biology
ADAM Proteins
Kidney Tubules
Basic Research
Endocrinology
Nephrology
Ureteric bud
Mutation
biology.protein
Amyloid Precursor Protein Secretases
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 10466673
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology
- Accession number :
- edsair.doi.dedup.....95f490a738b5a9c776c00588e2c7b80c