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2021 Fiscal Year Final Research Report

Creation of a Mutant EDA for the Treatment of Preterm Birth

Research Project

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Project/Area Number 19K09801
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionKyoto University

Principal Investigator

Chigusa Yoshitsugu  京都大学, 医学研究科, 助教 (80779158)

Co-Investigator(Kenkyū-buntansha) 近藤 英治  京都大学, 医学研究科, 准教授 (10544950)
最上 晴太  京都大学, 医学研究科, 講師 (40378766)
Project Period (FY) 2019-04-01 – 2022-03-31
Keywords早産 / 羊膜
Outline of Final Research Achievements

Extra domain A (EDA), which is contained in fetal fibronectin in vaginal secretions, binds to TLR4 in amniotic mesenchymal cells and promotes the production of COX-2 and MMPs, thereby inducing preterm labor. In this study, we aimed to identify the amino acid residues essential for EDA-TLR4 binding and to create mutant EDA with modifications of these residues. First, the 90 amino acid sequence comprising EDA was divided into four parts, and EDA with each amino acid deleted was created. As a result, EDAs with deletions of seven specific amino acids failed to bind to TLR4. Among them, when tyrosine 36 was mutated, EDA did not bind to TRL4. In other words, of the 90 amino acids in EDA, tyrosine 36 was found to be essential for binding to TLR4.

Free Research Field

周産期医学

Academic Significance and Societal Importance of the Research Achievements

早産のマーカーとして知られるフィブロネクチンが羊膜と作用して早産を惹起するメカニズムの一端を解明した。特に、フィブロネクチン中のEDAを構成するわずか1つのアミノ酸(チロシン36)が、羊膜間葉細胞のTLR4との結合に必須であることを明らかにしたことは、学術的に価値がある。今後、このチロシン36は早産予防、治療のための新規薬剤開発の標的となり、全身への副作用が少ない画期的な薬剤創出につながる可能性がある。早産は新生児死亡、後遺症の重要な原因であり、早産の予防・治療は周産期医学領域における喫緊の課題であることから、早産治療薬の創出は社会的意義が大きい。

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Published: 2023-01-30  

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