Elucidation of RAGE-Mediated Glucocorticoid / Inflammation-Driven Muscle Atrophy Mechanisms and Development of Novel Therapies.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07879
• 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: Hyogo Medical University
• Principal Investigator: Shoji Takuhito 兵庫医科大学, 医学部, 講師 (40624044)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: RAGE / 骨格筋 / ステロイド / 筋萎縮 / グルココルチコイド

Outline of Final Research Achievements

In this study, we examined the involvement of receptor for advanced glycation end products (RAGE) in skeletal muscle atrophy induced by glucocorticoid.
In vivo, 8 week-old mice were challenged with dexamethasone (DEX) for 4 weeks and compared the gastrocnemius muscle mass / body weight ratio between wild-type mice (WT) and RAGE-deficient mice (KO). In WT mice, DEX loading resulted in a significantly lower gastrocnemius muscle mass / body weight ratio compared to WT control, whereas DEX loading of KO mice resulted in a rather higher value compared to KO control. Skeletal muscle gene expression analysis after DEX loading suggested the involvement of Klf15 and REDD1, which are involved in steroid muscle atrophy, and RAGE-mediated skeletal muscle atrophy was considered to be mediated by these pathways.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会を迎えた日本において、筋萎縮・サルコペニアの克服は、高齢者のQOLを格段に向上させるのみならず、日本社会全体へ利益をもたらす。筋萎縮・サルコペニアに関する研究は、筋タンパクの異化/同化バランスの異化側へのシフト、筋修復能の低下、慢性炎症の持続などを中心に重要な知見が集積されつつある。近年増加している糖尿病や肥満は慢性炎症や酸化ストレス・AGE蓄積を通じて筋肉量低下や筋萎縮に影響する。一方、グルココルチコイドによる筋萎縮の病態解明も進んできているが、解明には至っておらず、我々の進めるRAGEによる筋萎縮の機序解明が、筋萎縮・サルコペニアの全体的な機序解明につながる一歩になる。