Sarcopenia in kidney dysfunction

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09316
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Wakayama Medical University
• Principal Investigator: OHYA Masaki 和歌山県立医科大学, 医学部, 講師 (90550301)
• Co-Investigator(Kenkyū-buntansha): 重松 隆 和歌山県立医科大学, 医学部, 教授 (30187348) ; 園生 智広 和歌山県立医科大学, 医学部, 博士研究員 (70614866)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: サルコペニア / 骨ミネラル代謝異常 / 慢性腎臓病 / 高リン血症

Outline of Final Research Achievements

The aim of this study was to determine the effect of hyperphosphatemia on skeletal muscle.Differentiated rat myoblast cells (L6) were used in this study. Cells were exposed to normal(CON),medium(MPi) and high (HPi) phosphate conditions for 10 days. We measured the protein levels of myosin heavy chain (MHC) and myostatin and determined the ratio of phosphorylated p70S6K and cleaved caspase-3 by western blot. The expression levels of the myogenic transcriptional regulators MyoD and myogenin were measured by qPCR.The levels of MHC were gradually downregulated depending on the phosphate concentration. Myostatin in HPi was about 20 times higher than in CON (P<0.001). In myotubes cultured in HPi, protein synthesis was significantly lower, and degradation was significantly higher than in CON (P<0.01). The mRNA expression of MyoD in HPi was significantly lower than in CON.This study showed that hyperphosphatemia strongly induced muscle atrophy with the accumulation of myostatin.

Free Research Field

慢性腎臓病に伴う骨ミネラル代謝異常

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会になる我が国において、Quality Of Life (QOL)を低下させるサルコペニアは一大問題として考えられており、近年の学術的なトピックとして様々な研究が活発に行われてきている。慢性腎臓病（CKD）患者において、ステージに依存してサルコペニア合併の頻度が高く、また、CKD患者での低骨格筋量は生命予後不良と関連しているという疫学的な研究結果が報告されている。したがって、CKDとサルコペニアのより生理学的な機序を明らかにすることは、予防・治療戦略を考える意味で重要であると考えられているが、まだまだ明らかにされていないのが現状である。