Downregulation of renal type IIa sodium-dependent phosphate cotransporter during lipopolysaccharide-induced acute inflammation

Am J Physiol Renal Physiol. 2014 Apr 1;306(7):F744-50. doi: 10.1152/ajprenal.00474.2013. Epub 2014 Feb 5.

Abstract

The type IIa sodium-dependent phosphate cotransporter (Npt2a) plays a critical role in reabsorption of inorganic phosphate (Pi) by renal proximal tubular cells. Pi abnormalities during early stages of sepsis have been reported, but the mechanisms regulating Pi homeostasis during acute inflammation are poorly understood. We examined the regulation of Pi metabolism and renal Npt2a expression during lipopolysaccharide (LPS)-induced inflammation in mice. Dose-response and time-course studies with LPS showed significant increases of plasma Pi and intact parathyroid hormone (iPTH) levels and renal Pi excretion, while renal calcium excretion was significantly decreased. There was no difference in plasma 1,25-dihydroxyvitamin D levels, but the induction of plasma intact fibroblast growth factor 23 levels peaked 3 h after LPS treatment. Western blotting, immunostaining, and quantitative real-time PCR showed that LPS administration significantly decreased Npt2a protein expression in the brush border membrane (BBM) 3 h after injection, but there was no change in renal Npt2a mRNA levels. Moreover, tumor necrosis factor-α injection also increased plasma iPTH and decreased renal BBM Npt2a expression. Importantly, we revealed that parathyroidectomized rats had impaired renal Pi excretion and BBM Npt2a expression in response to LPS. These results suggest that the downregulation of Npt2a expression in renal BBM through induction of plasma iPTH levels alter Pi homeostasis during LPS-induced acute inflammation.

Keywords: LPS; Npt2a; PTH; kidney; phosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Calcium / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Fibroblast Growth Factors / blood
  • Inflammation / blood
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Injections, Intraperitoneal
  • Kidney / metabolism*
  • Lipopolysaccharides*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Microvilli / metabolism
  • Parathyroid Hormone / blood
  • Parathyroidectomy
  • Phosphates / blood
  • Phosphates / metabolism*
  • Phosphates / urine
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / genetics
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / metabolism*
  • Time Factors
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood

Substances

  • Lipopolysaccharides
  • Parathyroid Hormone
  • Phosphates
  • RNA, Messenger
  • Slc34a1 protein, mouse
  • Slc34a1 protein, rat
  • Sodium-Phosphate Cotransporter Proteins, Type IIa
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide, E coli O55-B5
  • Vitamin D
  • Fibroblast Growth Factors
  • 1,25-dihydroxyvitamin D
  • fibroblast growth factor 23
  • Calcium