Analysis of calcium-dependent signaling in regulation of skeletal muscle mass

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17534
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kobe University
• Principal Investigator: HIRATA Yu 神戸大学, 医学研究科, 医学研究員 (70846352)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 骨格筋 / 不動化性筋萎縮 / KLF15

Outline of Final Research Achievements

We have analyzed the molecular mechanism of skeletal muscle atrophy due to immobilization. Transcription factor KLF15 is an important regulator in immobilization-induced muscle atrophy. It was revealed that a decline in intracellular Ca2+ concentration from the basal level is involved in an upstream regulatory mechanism of KLF15. We also identified Piezo1, a mechanosensor, as the responsible Ca2+ channel for immobilization-induced muscle atrophy. We thus revealed that a decrease in Ca2+ signaling of muscle cells, which is caused by a reduction in expression of the Piezo1 channel, triggers immobilization-induced muscle loss through the action of KLF15.

Free Research Field

糖尿病代謝学

Academic Significance and Societal Importance of the Research Achievements

不動化では基底状態以下へのCa2+濃度の低下が筋萎縮の引き金になると考えられたが、Ca2+濃度が「基底状態以下に低下」することによって発動する生命現象を初めて同定した。また、新規に確立した骨格筋Ca2+バイオイメージング法は各種の筋・神経疾患の研究に応用できる可能性があり、本研究によって同定されたPiezo1/KLF15経路は運動とは独立した不動化固有のシグナルであることから、新規な観点からの筋萎縮抑制薬の開発に繋がる可能性があると考えられた。