Abstract
The mechanism by which phosphorus levels are maintained in the body was investigated by analyzing changes in gene expression in the rat kidney following administration of a high phosphorus (HP) diet. Male Wistar rats were divided into two groups and fed a diet containing 0.3% (control) or 1.2% (HP) phosphorous for 24 days. Phosphorous retention was not significantly increased in HP rats, but fractional excretion of phosphorus was significantly increased in the HP group compared to controls, with an excessive amount of the ingested phosphorus being passed through the body. DNA microarray analysis of kidney tissue from both groups revealed changes in gene expression profile induced by a HP diet. Among the genes that were upregulated, Gene Ontology (GO) terms related to ossification, collagen fibril organization, and inflammation and immune response were significantly enriched. In particular, there was significant upregulation of type IIb sodium-dependent phosphate transporter (NaPi-IIb) in the HP rat kidney compared to control rats. This upregulation was confirmed by in situ hybridization. Distinct signals for NaPi-IIb in both the cortex and medulla of the kidney were apparent in the HP group, while the corresponding signals were much weaker in the control group. Immunohistochemical analysis showed that NaPi-IIb localized to the basolateral side of kidney epithelial cells surrounding the urinary duct in HP rats but not in control animals. These data suggest that NaPi-IIb is upregulated in the kidney in response to the active excretion of phosphate in HP diet-fed rats.
Highlights
Phosphorus is an important factor in numerous biological processes and exists in the form of inorganic phosphates in the body
Applying a significance value for the false discovery rate (FDR) of,0.05, we identified 1056 upregulated probe sets (838 genes) and 712 downregulated probe sets (536 genes) in the high phosphorus (HP) group compared to the control group
DNA microarray analysis was used to investigate the effects of a HP diet on gene expression in the rat kidney
Summary
Phosphorus is an important factor in numerous biological processes and exists in the form of inorganic phosphates in the body. The intake of dietary phosphate has been gradually increasing with changes in life style over the past several decades [1]. Present-day levels of dietary phosphate are not likely to cause imminent hyperphosphatemia; excessive intake could present serious problems, for chronic renal patients. Our understanding of the mechanisms of phosphate homeostasis is extremely important. The major organs involved in phosphate homeostasis are the small intestine, kidney, parathyroid gland, and bone. Serum phosphate levels are tightly-regulated through the action of humoral factors such as parathyroid hormone (PTH), fibroblast growth factor 23, and 1a,25-dihydroxyvitamine D ( known as calcitriol). The expression or synthesis of these factors is coordinately regulated in response to changes in dietary and serum phosphate levels [2]. The mechanism of regulation of phosphate homeostasis, including effector molecules such as phosphate transporters, remains to be elucidated
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