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

研究成果: Article

20 引用 (Scopus)

抄録

Uptake of P i 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 P i transporter Pit-1 to explore the role of extracellular P i 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 P i uptake in podocytes than wild-type rats, especially under low P i 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.

元の言語English
ページ(範囲)848-856
ページ数9
ジャーナルAmerican Journal of Physiology - Renal Physiology
300
発行部数4
DOI
出版物ステータスPublished - 01-04-2011
外部発表Yes

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Phosphate Transport Proteins
Transgenic Rats
Podocytes
Phosphates
Wounds and Injuries
Sclerosis
Glomerular Basement Membrane
Diet
Proteinuria
Kidney
Hypoalbuminemia
Connexin 43
Cachexia
Dyslipidemias
Transmission Electron Microscopy
Chronic Renal Insufficiency
Foot
Creatinine
Cell Survival
Maintenance

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

これを引用

Sekiguchi, Sahoko ; Suzuki, Atsushi ; Asano, Shogo ; Nishiwaki-Yasuda, Keiko ; Shibata, Megumi ; Nagao, Shizuko ; Yamamoto, Naoki ; Matsuyama, Mutsushi ; Sato, Yutaka ; Yan, Kunimasa ; Yaoita, Eishin ; Itoh, Mitsuyasu. / Phosphate overload induces podocyte injury via type III Na-dependent phosphate transporter. :: American Journal of Physiology - Renal Physiology. 2011 ; 巻 300, 番号 4. pp. 848-856.
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abstract = "Uptake of P i 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 P i transporter Pit-1 to explore the role of extracellular P i 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 P i uptake in podocytes than wild-type rats, especially under low P i 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.",
author = "Sahoko Sekiguchi and Atsushi Suzuki and Shogo Asano and Keiko Nishiwaki-Yasuda and Megumi Shibata and Shizuko Nagao and Naoki Yamamoto and Mutsushi Matsuyama and Yutaka Sato and Kunimasa Yan and Eishin Yaoita and Mitsuyasu Itoh",
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Sekiguchi, S, Suzuki, A, Asano, S, Nishiwaki-Yasuda, K, Shibata, M, Nagao, S, Yamamoto, N, Matsuyama, M, Sato, Y, Yan, K, Yaoita, E & Itoh, M 2011, 'Phosphate overload induces podocyte injury via type III Na-dependent phosphate transporter', American Journal of Physiology - Renal Physiology, 巻. 300, 番号 4, pp. 848-856. https://doi.org/10.1152/ajprenal.00334.2010

Phosphate overload induces podocyte injury via type III Na-dependent phosphate transporter. / Sekiguchi, Sahoko; Suzuki, Atsushi; Asano, Shogo; Nishiwaki-Yasuda, Keiko; Shibata, Megumi; Nagao, Shizuko; Yamamoto, Naoki; Matsuyama, Mutsushi; Sato, Yutaka; Yan, Kunimasa; Yaoita, Eishin; Itoh, Mitsuyasu.

:: American Journal of Physiology - Renal Physiology, 巻 300, 番号 4, 01.04.2011, p. 848-856.

研究成果: Article

TY - JOUR

T1 - Phosphate overload induces podocyte injury via type III Na-dependent phosphate transporter

AU - Sekiguchi, Sahoko

AU - Suzuki, Atsushi

AU - Asano, Shogo

AU - Nishiwaki-Yasuda, Keiko

AU - Shibata, Megumi

AU - Nagao, Shizuko

AU - Yamamoto, Naoki

AU - Matsuyama, Mutsushi

AU - Sato, Yutaka

AU - Yan, Kunimasa

AU - Yaoita, Eishin

AU - Itoh, Mitsuyasu

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Uptake of P i 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 P i transporter Pit-1 to explore the role of extracellular P i 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 P i uptake in podocytes than wild-type rats, especially under low P i 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.

AB - Uptake of P i 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 P i transporter Pit-1 to explore the role of extracellular P i 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 P i uptake in podocytes than wild-type rats, especially under low P i 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.

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