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Prorenin receptor is critical for nephron progenitors.
- Source :
-
Developmental biology [Dev Biol] 2016 Jan 15; Vol. 409 (2), pp. 382-91. Date of Electronic Publication: 2015 Dec 03. - Publication Year :
- 2016
-
Abstract
- Deficient nephrogenesis is the major factor contributing to renal hypoplasia defined as abnormally small kidneys. Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H(+)-ATPase. Global loss of PRR is lethal in mice and PRR mutations are associated with a high blood pressure, left ventricular hypertrophy and X-linked mental retardation in humans. To circumvent lethality of the ubiquitous PRR mutation in mice and to determine the potential role of the PRR in nephrogenesis, we generated a mouse model with a conditional deletion of the PRR in Six2(+) nephron progenitors and their epithelial derivatives (Six2(PRR-/-)). Targeted ablation of PRR in Six2(+) nephron progenitors caused a marked decrease in the number of developing nephrons, small cystic kidneys and podocyte foot process effacement at birth, and early postnatal death. Reduced congenital nephron endowment resulted from premature depletion of nephron progenitor cell population due to impaired progenitor cell proliferation and loss of normal molecular inductive response to canonical Wnt/β-catenin signaling within the metanephric mesenchyme. At 2 months of age, heterozygous Six2(PRR+/-) mice exhibited focal glomerulosclerosis, decreased kidney function and massive proteinuria. Collectively, these findings demonstrate a cell-autonomous requirement for the PRR within nephron progenitors for progenitor maintenance, progression of nephrogenesis, normal kidney development and function.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Death
Cell Proliferation
Epithelium embryology
Gene Deletion
Gene Dosage
Gene Targeting
Homeodomain Proteins metabolism
Kidney cytology
Kidney embryology
Kidney physiopathology
Kidney Diseases, Cystic complications
Kidney Diseases, Cystic pathology
Kidney Diseases, Cystic physiopathology
Mesoderm cytology
Mesoderm embryology
Mice
Organogenesis
Podocytes metabolism
Podocytes ultrastructure
Proteinuria complications
Proteinuria physiopathology
Receptors, Cell Surface deficiency
Receptors, Cell Surface genetics
Stem Cells metabolism
Transcription Factors metabolism
Prorenin Receptor
Nephrons cytology
Receptors, Cell Surface metabolism
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-564X
- Volume :
- 409
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 26658320
- Full Text :
- https://doi.org/10.1016/j.ydbio.2015.11.024