• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2023 Fiscal Year Final Research Report

Inflammatory cytokine-induced muscle atrophy and weakness can be ameliorated by an inhibition of TGF-beta-activated kinase-1

Research Project

  • PDF
Project/Area Number 21K07339
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionThe University of Tokushima

Principal Investigator

ENDO Itsuro  徳島大学, 大学院医歯薬学研究部(医学域), 教授 (10432759)

Co-Investigator(Kenkyū-buntansha) 倉橋 清衛  徳島大学, 大学院医歯薬学研究部(医学域), 特任講師 (30567342)
安倍 正博  徳島大学, 大学院医歯薬学研究部(医学域), 教授 (80263812)
金井 麻衣  徳島大学, 大学院医歯薬学研究部(医学域), 助教 (90836470)
Project Period (FY) 2021-04-01 – 2024-03-31
KeywordsTAK1阻害 / 炎症性サイトカイン / 骨格筋萎縮
Outline of Final Research Achievements

TGF-beta-activated kinase-1 (TAK1) mediates most inflammatory cytokine signals that causes muscle wasting. This study was undertaken to clarify whether TAK1 inhibition can ameliorate inflammation-induced muscle wasting. SKG/Jcl mice, an autoimmune arthritis model, were treated with an adjuvant, mannan, to enhance production of TNF-alpha and IL-1beta These cytokines reduced muscle mass and strength via phosphorylation of TAK1, that activated NF-kappaB, p38 MAPK, ERK pathways and enhanced myostatin expression. Myostatin reduced MyoD1 and enhanced Atrogin-1 and Murf1 expression to cause muscle wasting. TAK1 inhibition by LL-Z1640-2 prevented muscle wasting, and can be a new therapeutic target of inflammation-induced muscle wasting.

Free Research Field

内分泌代謝、骨カルシウム代謝

Academic Significance and Societal Importance of the Research Achievements

炎症性サイトカイン過剰による慢性炎症は骨格筋量の減少や筋力低下の原因となり、加齢によるサルコペニアの病態にも関連する。我々は、TGF-beta activated kinase 1 (TAK1)阻害が複数の炎症性サイトカインの細胞内シグナル伝達を抑制して抗炎症作用を発揮するという背景に基づき、TAK1阻害薬(LLZ)が炎症性サイトカイン誘導性の筋萎縮・筋力低下を改善できることをin vivoおよびin vitroの系で示した。以上の検討結果より、TAK1阻害は炎症性サイトカイン誘導性筋障害の治療ターゲットたり得る可能性があることが示された。

URL: 

Published: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi