論文

査読有り 国際誌
2019年6月

Regulation of α-Klotho Expression by Dietary Phosphate During Growth Periods.

Calcified tissue international
  • Shiori Fukuda-Tatano
  • ,
  • Hironori Yamamoto
  • ,
  • Otoki Nakahashi
  • ,
  • Ryouhei Yoshikawa
  • ,
  • Mayu Hayashi
  • ,
  • Maki Kishimoto
  • ,
  • Yukiko Imi
  • ,
  • Hisami Yamanaka-Okumura
  • ,
  • Kohta Ohnishi
  • ,
  • Masashi Masuda
  • ,
  • Yutaka Taketani

104
6
開始ページ
667
終了ページ
678
記述言語
英語
掲載種別
DOI
10.1007/s00223-019-00525-0

Inorganic phosphate (Pi) is an essential nutrient for maintaining various biological functions, particularly during growth periods. Excess intake of dietary Pi increases the secretion of fibroblast growth factor 23 (FGF23) and parathyroid hormone to maintain plasma Pi levels. FGF23 is a potent phosphaturic factor that binds to the α-klotho/FGFR complex in the kidney to promote excretion of Pi into the urine. In addition, excess intake of dietary Pi decreases renal α-klotho expression. Down-regulation or lack of α-klotho induces a premature aging-like phenotype, resulting from hyperphosphatemia, and leading to conditions such as ectopic calcification and osteoporosis. However, it remains unclear what effects dietary Pi has on α-klotho expression at different life stages, especially during growth periods. To investigate this, we used C57BL/6J mice in two life stages during growing period. Weaned (3 weeks old) and periadolescent (7 weeks old) were randomly divided into seven experimental groups and fed with 0.02, 0.3, 0.6, 0.9, 1.2, 1.5, or 1.8% Pi diets for 7 days. As a result, elevated plasma Pi and FGF23 levels and decreased renal α-klotho expression were observed in weaned mice fed with a high Pi diet. In addition, a high Pi diet clearly induced renal calcification in the weaned mice. However, in the periadolescent group, renal calcification was not observed, even in the 1.8% Pi diet group. The present study indicates that a high Pi diet in weaned mice has much greater adverse effects on renal α-klotho expression and pathogenesis of renal calcification compared with periadolescent mice.

リンク情報
DOI
https://doi.org/10.1007/s00223-019-00525-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30671592
ID情報
  • DOI : 10.1007/s00223-019-00525-0
  • PubMed ID : 30671592

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