Protein Kinase C mediated alteration of placental angiogenic and antiangiogenic factors in pregnancy complicated with diabetes mellitus

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K18697
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Okayama University
• Principal Investigator: Mitsui Takashi 岡山大学, 大学病院, 助教 (60769008)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 糖尿病合併妊娠 / 妊娠高血圧腎症

Outline of Final Research Achievements

Pregnancies were established in diabetic model mice, and the progression to preeclampsia was monitored using blood pressure measurements and proteinuria tests. The angiogenic and anti-angiogenic factors were evaluated. The activated state of PKCβ was also examined in placental tissue. Furthermore, we administered a PKCβ inhibitor to a mouse model of pregnancy with diabetes and examined its changes.
As a result of the experiment, we observed a significant increase in the activation of PKCβ in the placenta in the diabetic pregnancy model mouse. In the placenta and maternal bloods, sFlt-1 increases, and PlGF decrease. Furthermore, it was possible to suppress these changes by administering a PKCβ inhibitor.

Free Research Field

周産期医学

Academic Significance and Societal Importance of the Research Achievements

妊娠高血圧腎症は、糖代謝異常合併妊娠に合併し、発症すると母体、胎児ともに重篤な合併症をもたらし、両者を死に至らす危険な疾患であるが、未だ有効な治療法が開発されていない。しかし、本研究成果から、PKCβがその病態の中心的分子であり、その異常活性化が、sFlt-1、PlGFのアンバランスを引き起こし、血管新生及び血管内皮障害を引き起こしている可能性を見出した。また、これらの変化はPCKβ特異的阻害剤を使用することにより抑制できた。
従って、本研究では糖代謝異常合併妊娠における妊娠高血圧腎症の発症及び増悪の機序の解明に貢献し、PKCβを標的とした治療応用への可能性を見出した。