Prorenin receptor controls renal branching morphogenesis via Wnt/β-catenin signaling
| Autor: | Adam Janssen, Yuwen Li, Samir S. El-Dahr, Renfang Song, Ihor V. Yosypiv |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glial Cell Line-Derived Neurotrophic Factor Receptors Genotype Physiology Bone Morphogenetic Protein 7 Wnt β catenin signaling Kidney development Receptors Cell Surface Cell Separation Biology 03 medical and health sciences Branching morphogenesis Renin–angiotensin system Morphogenesis Animals Cell Lineage Gene Regulatory Networks Prorenin Receptor Kidney Tubules Collecting Receptor Fibroblast Growth Factor Type 2 Receptor Wnt Signaling Pathway beta Catenin Mice Knockout Genetics ATP6AP2 Proto-Oncogene Proteins c-ets Gene Expression Profiling Computational Biology Gene Expression Regulation Developmental Cell Differentiation Flow Cytometry Cell biology Wnt Proteins Phenotype 030104 developmental biology Animals Newborn Ureteric bud Ureter Transcriptome Accessory subunit |
| Zdroj: | American Journal of Physiology-Renal Physiology. 312:F407-F417 |
| ISSN: | 1522-1466 1931-857X |
| Popis: | The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H+-ATPase. Renal branching morphogenesis, defined as growth and branching of the ureteric bud (UB), is essential for mammalian kidney development. Previously, we demonstrated that conditional ablation of the PRR in the UB in PRRUB−/−mice causes severe defects in UB branching, resulting in marked kidney hypoplasia at birth. Here, we investigated the UB transcriptome using whole genome-based analysis of gene expression in UB cells, FACS-isolated from PRRUB−/−, and control kidneys at birth (P0) to determine the primary role of the PRR in terminal differentiation and growth of UB-derived collecting ducts. Three genes with expression in UB cells that previously shown to regulate UB branching morphogenesis, including Wnt9b, β-catenin, and Fgfr2, were upregulated, whereas the expression of Wnt11, Bmp7, Etv4, and Gfrα1 was downregulated. We next demonstrated that infection of immortalized UB cells with shPRR in vitro or deletion of the UB PRR in double-transgenic PRRUB−/−/ BatGal+mice, a reporter strain for β-catenin transcriptional activity, in vivo increases β-catenin activity in the UB epithelia. In addition to UB morphogenetic genes, the functional groups of differentially expressed genes within the downregulated gene set included genes involved in molecular transport, metabolic disease, amino acid metabolism, and energy production. Together, these data demonstrate that UB PRR performs essential functions during UB branching and collecting duct morphogenesis via control of a hierarchy of genes that control UB branching and terminal differentiation of the collecting duct cells. |
| Databáze: | OpenAIRE |
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