Research for the pathogenesis of kaposiform lymphangiomatosis in PIK3CA/RAS signal pathway

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07838
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Gifu University
• Principal Investigator: Ozeki Michio 岐阜大学, 医学部附属病院, 講師 (60444303)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: リンパ管腫症

Outline of Final Research Achievements

Kaposiform lymphangiomatosis is a progressive, rare, and difficult-to-treat type of lymphangiomatosis that involves the proliferation of lymphatic tissue throughout the body. Recently, genetic mutations in the 'PIK3/RAS signaling' pathway, which is important for angiogenesis and lymphangiogenesis, have been detected in the affected areas, but it is unclear how these genetic abnormalities lead to clinical symptoms. In this study, the NRAS (Q61R) gene mutation was introduced into human lymphatic endothelial cells, and cell proliferation ability was measured using the MTT assay, as well as Real-time PCR and Western blot analysis, and the effects of inhibitors were tested. Additionally, a transgenic mouse expressing the NRAS Q61R mutation in lymphatic endothelial cells was created.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

リンパ管腫症の中でも非常に予後が悪く、治療抵抗性であるカポジ型リンパ管腫症の病態マ解明に繋がる研究を行った。最近では、ｍTOR阻害剤がリンパ管腫症に対する新規治療薬として薬事承認されたが、いまだ治療抵抗性で亡くなる症例も多い。今回の病態解明によって、NRAS変異が病態に関与すること、および新規治療薬に繋がる研究結果を得た。今後はその候補となる薬剤の臨床応用を検討している。