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2021 Fiscal Year Final Research Report

Mechanism of protein secretion by physical stimuli (turbulent) and its physiological significance

Research Project

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Project/Area Number 20K21523
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionShiga University of Medical Science

Principal Investigator

Nishi Eiichiro  滋賀医科大学, 医学部, 教授 (30362528)

Project Period (FY) 2020-07-30 – 2022-03-31
Keywordsナルディライジン / 物理刺激 / タンパク質分泌 / 血小板 / ペプチダーゼ
Outline of Final Research Achievements

Physical stimuli such as pressure, shear stress, and temperature are spatiotemporally regulated in vivo and are presumably involved in various homeostasis. We have shown that turbulent induces nardilysin (NRDC) secretion from iPS cell-derived megakaryocytes (imMKCL) and that NRDCs induce platelet production in a peptidase activity-dependent manner (Cell 2018). To clarify the causal relationship between turbulent-induced NRDC secretion and platelet production and the mechanism by which the peptidase activity contributes, we have generated NRDC-deficient imMKCL, megakaryocyte-specific NRDC-deficient mice and peptidase-inactive Nrdc knock-in mice, and examined the process of platelet production.

Free Research Field

病態医化学 薬理学 内科学

Academic Significance and Societal Importance of the Research Achievements

体内の細胞は、常に温度や圧力などの物理的刺激を受けています。これらの刺激を感知する受容体の発見に対して、2021年にノーベル医学生理学賞が授与されましたが、物理的刺激の生理病理学的役割はまだよくわかっていません。私たちは、物理的刺激のひとつである乱流が、NRDCというタンパク質の分泌を増やし、その結果血小板の産生が増えることを見出しました。本研究は、そのくわしいしくみを明らかにし、ひいては血小板減少症の治療につなげることを目的にして行いました。

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Published: 2023-01-30  

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