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

• 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. Microarray expression data of key transcripts were verified by real-time RT-PCR analysis. RESULTS: Several genes that play a role in Pi regulation revealed decreased expression levels in the transgenic mice, such as Npt2a and Pdzk1, a scaffolding protein known to interact with Npt2a. Importantly, Klotho, a suggested FGF23 receptor cofactor, was the most significantly decreased transcript and alpha2-Na(+)/K(+)-ATPase (Atp1a2), a gene isoform of alpha1-Na(+)/K(+)-ATPase (Atp1a1) which has recently been shown to interact with Klotho and regulate calcium metabolism, was the most increased transcript. In contrast, other genes proposed to regulate Pi levels, such as secreted frizzled-related protein-4 (sFrp4) and Na(+)/H(+) exchanger regulatory factor-1 (Nherf1) revealed no changes. CONCLUSIONS: FGF23 transgenic mice display differentially expressed transcript levels of several genes essential in renal Pi regulation. These findings may lead to further understanding of how FGF23 mediates its actions on renal Pi regulation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

Nyckelord

Animals

Calcium

metabolism

Fibroblast Growth Factors

genetics

metabolism

Gene Expression Profiling

Homeostasis

physiology

Intracellular Signaling Peptides and Proteins

genetics

metabolism

Kidney

metabolism

pathology

Mice

Mice

Transgenic

Oligonucleotide Array Sequence Analysis

Phosphates

metabolism

Phosphoproteins

genetics

metabolism

RNA

Messenger

Sodium-Hydrogen Antiporter

genetics

metabolism

Sodium-Phosphate Cotransporter Proteins

Type IIa

genetics

metabolism

Sodium-Potassium-Exchanging ATPase

genetics

metabolism

MEDICINE

Orthopaedics

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)