Functional analysis of novel skeletal muscle cell-secreted protein aiming for the establishment of novel therapeutic strategies for sarcopenia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07810
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: International University of Health and Welfare
• Principal Investigator: Takemoto Minoru 国際医療福祉大学, 医学部, 主任教授 (60447307)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: サルコペニア / マイオカイン / 自己抗体

Outline of Final Research Achievements

Age-related sarcopenia is a risk factor that hinders healthy longevity. Sarcopenia is associated with age-related declining in skeletal muscle regenerative capacity that substantially impairs daily lifestyle activities in the elderly. The proliferation and differentiation of muscle satellite cells are critical for skeletal muscle regeneration. We discovered a new protein called R3h domain containing-like (R3hdml), which is secreted by satellite cells and promotes the proliferation and differentiation of muscle satellite cells. In this study, autoantibodies that inhibit R3hdml action were found to be more prevalent in patients with diabetes, dyslipidemia, fatty liver, obesity, and chronic kidney disease. Inhibiting R3hdml's physiological action may promote sarcopenia through lifestyle-related diseases or by inhibiting the proliferation and differentiation of muscle satellite cells.

Free Research Field

糖尿病・代謝

Academic Significance and Societal Importance of the Research Achievements

昨年度はR3hdmlに対する自己抗体が慢性腎臓病患者で増加していることを明らかにした。R3hdmlはTGFβ-p38MAPK経路を抑制し、ポドサイトのアポトーシスを抑制する（J Mol Med (Berl). 2021）。今年度の成果によりR3hdml抗体は糖尿病をはじめとした様々な生活習慣病で上昇していることを明らかにした。この上昇したR3hdml抗体は生活習慣病を通じて、もしくは直接、筋衛星細胞の増殖・分化阻害することでサルコペニアを助長する可能性がある。今後、R3hdml抗体に対する介入をすることで、将来のサルコペニア予防のための新たな治療法開発につながる可能性がある。