Phosphate overload induces podocyte injury via type III Na-dependent phosphate transporter

Sahoko Sekiguchi, Atsushi Suzuki, Shogo Asano, Keiko Nishiwaki-Yasuda, Megumi Shibata, Shizuko Nagao, Naoki Yamamoto, Mutsushi Matsuyama, Yutaka Sato, Kunimasa Yan, Eishin Yaoita, Mitsuyasu Itoh

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Uptake of Pi at the cellular membrane is essential for the maintenance of cell viability. However, phosphate overload is also stressful for cells and can result in cellular damage. In the present study, we investigated the effects of the transgenic overexpression of type III Pi transporter Pit-1 to explore the role of extracellular Pi in glomerular sclerosis during chronic renal disease. Pit-1 transgenic (TG) rats showed progressive proteinuria associated with hypoalbuminemia and dyslipidemia. Ultrastructural analysis of TG rat kidney by transmission electron microscopy showed a diffuse effacement of the foot processes of podocytes and a thickening of the glomerular basement membrane, which were progressively exhibited since 8 wk after birth. TG rats died at 32 wk of age due to cachexia. At this time, more thickening of the glomerular basement membrane and segmental sclerosis were observed in glom-eruli of the TG rats. Immunohistochemical examination using anti-connexin 43 and anti-desmin antibodies suggested the progressive injury of podocytes in TG rats. TG rats showed higher Pi uptake in podocytes than wild-type rats, especially under low Pi concentration. When 8-wk-old wild-type and TG rats were fed a 0.6% normal phosphate (NP) or 1.2% phosphate (HP) diet for 12 wk, HP diet-treated TG rats showed more progressive proteinuria and higher serum creatinine levels than NP diet-treated TG rats. In conclusion, our findings suggest that overexpression of Pit-1 in rats induces phosphate-dependent podocyte injury and damage to the glomerular barrier, which result in the progression of glomerular sclerosis in the kidney.

Original languageEnglish
Pages (from-to)848-856
Number of pages9
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number4
DOIs
Publication statusPublished - 01-04-2011

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

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