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The role of O-GlcNAcylation on Notch1 in the self-renewal of muscle satellite cells

Research Project

Project/Area Number 19K16517
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionNagoya University

Principal Investigator

LO PEIWEN  名古屋大学, 医学系研究科, 研究機関研究員 (20822406)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Discontinued (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
KeywordsO-GlcNAcylation / Notch1 / aging / muscle / satellite cell / regeneration / skeletal muscle
Outline of Research at the Start

Muscle regeneration declines with aging and interferes life of numerous aged people. Nevertheless, the therapy for ameliorating degeneracy of muscle regeneration is limited thus far. It has been known that Notch1 contributes to decline of muscle regeneration with aging and O-GlcNAcylation, implicates in Notch1 signaling pathway. Thus, we speculate that O-GlcNAcylation may be involved with muscle regeneration via Notch1 protein. We expect this study could be conductive to the improvement of muscle rejuvenation for aged people and the therapy for muscular dystrophy patients.

Outline of Annual Research Achievements

We speculated declined muscle self-renewal with aging is mediated partially by the O-GlcNAcylation on Notch1.
To understand if the O-GlcNAcylation status of Notch1 is altered with aging, I established the inducible FLAG-Notch1 transgenic mice. Afterwards, O-GlcNAcylation on Notch1 protein extracted from aged and younger mice will be applied in glycosylation analysis.
Albeit Eogt didn’t be detected in satellite cells of muscle, I found Eogt distributes only in “certain” myofibers. In further experiments, I found Eogt highly overlaps myofiber type2A.
The mouse hanging assay also shows Eogt knockdown reduces muscle contractibility.
It suggests that Eogt is involved in muscle contractibility by mediating myofiber types. This study facilitates to ameliorate mobility of aged people.

Report

(2 results)
  • 2020 Annual Research Report
  • 2019 Research-status Report

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Published: 2019-04-18   Modified: 2021-12-27  

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