Interaction of klotho/megalin/NaPi2a, a novel regulating mechanism of phosphate homeostasis.

• Project/Area Number: 25870253
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology; Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: Kuwahara Shoji 新潟大学, 医歯(薬)学総合研究科, 特任助教 (70645209)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: リン代謝 / klotho / メガリン / エンドサイトーシス / 腎臓 / リン代謝調節 / megalinとklotho代謝 / megalinとリン代謝調節

Outline of Final Research Achievements

In our pilot study, we revealed that serum klotho levels were increased in our novel kidney specific megalin knock out (KO) mice, but we failed to reconfirm it. On the other hand, klotho was detected as cleaved form in urine only in megalin KO mice. And we found the interaction of klotho with megain by use of quartz crystal microbalance. These results mean klotho is one of the ligand of megalin and taken up by megalin into the proximal tubule cells.
Moreover, we investigated weather exogenous klotho can rescue phosphate excretion in klotho KO mice. Then, we found not only single administration of extracellular domain but also combined administration of KL1 and KL2 domain had phosphaturic effect.