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

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2008-03, Vol.23 (3), p.827-833
• Main Authors: Marsell, Richard, Krajisnik, Tijana, Göransson, Hanna, Ohlsson, Claes, Ljunggren, Östen, Larsson, Tobias E., Jonsson, Kenneth B.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Atp1a1; Atp1a2; Biological and medical sciences; Calcium; Calcium - metabolism; Emergency and intensive care: renal failure. Dialysis management; FGF-23; Fibroblast Growth Factors; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Gene Expression Profiling; genetics; Glomerulonephritis; Homeostasis; Homeostasis - physiology; Intensive care medicine; Intracellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kidney; Kidney - metabolism; Kidney - pathology; Kirurgi; Kirurgisk forskning; Klotho; MEDICAL AND HEALTH SCIENCES; Medical sciences; MEDICIN; MEDICIN OCH HÄLSOVETENSKAP; MEDICINE; Messenger; metabolism; Mice; Mice, Transgenic; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Oligonucleotide Array Sequence Analysis; Orthopaedics; Ortopedi; pathology; phosphate; Phosphates; Phosphates - metabolism; Phosphoproteins; Phosphoproteins - genetics; Phosphoproteins - metabolism; physiology; RNA; RNA, Messenger; Sodium-Hydrogen Antiporter; Sodium-Hydrogen Exchangers - genetics; Sodium-Hydrogen Exchangers - metabolism; Sodium-Phosphate Cotransporter Proteins; Sodium-Phosphate Cotransporter Proteins, Type IIa - genetics; Sodium-Phosphate Cotransporter Proteins, Type IIa - metabolism; Sodium-Potassium-Exchanging ATPase; Sodium-Potassium-Exchanging ATPase - genetics; Sodium-Potassium-Exchanging ATPase - metabolism; Surgery; Surgical research; Transgenic; Type IIa
• ISSN: 0931-0509; 1460-2385; 1460-2385
• DOI: 10.1093/ndt/gfm672

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 α1 (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 α2-Na+/K+-ATPase (Atp1a2), a gene isoform of α1-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.