The pathogenesis of preeclampsia focusing on the vascular endothelial dysfunction by HMGB1 and the search for new therapeutic agents.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: International University of Health and Welfare (2022-2023); The University of Tokyo (2021)
• Principal Investigator: Nagamatsu Takeshi 国際医療福祉大学, 国際医療福祉大学成田病院, 教授 (60463858)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 妊娠高血圧腎症 / HMGB1 / トロンボモジュリン / 妊娠 / 治療

Outline of Final Research Achievements

This study aimed to clarify the involvement of high-mobility group box 1 (HMGB1)in the pathogenesis of preeclampsia (PE)and to explore novel therapeutic approaches to PE by HMGB1 antagonism. In a mouse model angiotensin II (AngII)-induced PE,HMGB1 released from the placenta increases sFlt-1 production and induces an increase in inflammatory cytokines in trophoblast vells, developing csystemic maternal symptoms. HMGB1 was significantly increased in the serum of PE pregnant women in late pregnancy and PE placentas showed extra-nuclear leakage from trophoblastic cells. Thrombomodulin (TM), an antagonist of HMGB1, when administered to the Ang II-induced PE mouse model, contributed to the suppression of PE development.In conclusion, HMGB1 released from trophoblast cells is a factor exacerbating maternal organ damage and placental dysfunction. Suppression of HMGB1 by TM could be a new therapeutic approach for PE.

Free Research Field

周産期医学

Academic Significance and Societal Importance of the Research Achievements

妊娠高血圧腎症(PE)の臨床管理において近年末梢血中のsFlt-1/PlGF比を用いた発症予測が行われるようになったが、発症後の母児の予後改善のための有効な治療法はいまだ確立していない。本研究の成果によりHMGB1がPE発症に関与する因子であることが解明されて、トロンボモジュリンを用いたHMGB1作用阻害による治療アプローチの可能性が示された。本研究の成果が、将来のPE治療法開発への端緒となることが期待される。