Transcriptomics

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Transcription profiling of mouse kidney from FGF23, TG and WT mice


ABSTRACT: Fibroblast growth factor-23 (FGF23), a circulating protein produced in bone, causes renal inorganic phosphate (Pi) wasting by down-regulation of sodium phosphate co-transporter 2a (Npt2a). The mechanism behind this action is unknown. We have previously generated transgenic mice (TG) expressing human wild-type FGF23 under the control of the α1 (I) collagen promoter. In this study we performed a large scale gene expression study of kidneys from TG mice and wild-type littermates. Several genes that play a role in Pi regulation had decreased expression levels, such as Npt2a, but also Pdzk1 which is a scaffolding protein known to interact with NPT2a. Importantly, the Klotho gene, a suggested crucial co-factor for FGF23 receptor binding and activation, was the most affected decreased gene. However, other genes proposed to regulate Pi levels, such as secreted Frizzled Related Protein 4 (sFRP4), Na+/H+ exchanger regulatory factor 1 (NHERF1) and the FGF-receptors 1-4, revealed no changes. Interestingly, expression levels of inflammatory response genes were increased and histological analysis revealed tubular nephropathy in the TG mice kidneys. In conclusion, FGF23 TG mice have altered kidney gene expression levels of several genes thought to be part of Pi homeostasis and an increase in inflammatory response genes, data supported by histological analysis. These findings may lead to further understanding of how FGF23 mediates its actions on renal Pi regulation. Experiment Overall Design: Five kidneys from FGF23 TG mice and five kidneys from WT littermates was used for Affymetrix Genechip analysis. One Genechip was used/animal. Animals were 8 weeks old when kidneys were collected.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus musculus  

SUBMITTER: Richard Marsell  

PROVIDER: E-GEOD-6979 | ArrayExpress | 2008-06-15

SECONDARY ACCESSION(S): GSE6979PRJNA99287

REPOSITORIES: GEO, ArrayExpress

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Publications

Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-23.

Marsell Richard R   Krajisnik Tijana T   Göransson Hanna H   Ohlsson Claes C   Ljunggren Osten O   Larsson Tobias E TE   Jonsson Kenneth B KB  

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20071002 3


BACKGROUND: Fibroblast growth factor-23 (FGF23), a circulating protein produced in bone, causes decreased renal inorganic phosphate (Pi) reabsorption by reducing the expression of the sodium phosphate cotransporter type 2a (Npt2a). We have previously generated transgenic mice expressing human wild-type (WT) FGF23 under the control of the alpha1 (I) collagen promoter. METHODS: In this study, we performed a large-scale gene expression study of kidneys from FGF23 transgenic mice and WT littermates.  ...[more]

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