Role of TP signaling in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08241
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kitasato University
• Principal Investigator: Hosono Kanako 北里大学, 医学部, 非常勤講師 (80532556)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: リンパ管新生 / TP受容体 / 慢性炎症 / ノックアウトマウス

Outline of Final Research Achievements

Lymphatic vessels in diaphragm are essential for draining the inflammatory fluid during peritonitis. In this study, we evaluated role of thromboxane A2 receptor (TP) signaling in enhancement of lymphangiogenesis in peritonitis. Peritonitis was induced by injections of LPS (25μg/mouse) into peritoneal cavities in male C57BL/6 mice. We evaluated lymphatic microvessel density in whole-mounted diaphragm tissues. A week after LPS application, expressions of COX-2, thromboxane synthase (TXS) and VEGF-C/D in diaphragm were up-regulated with increment of lymphangiogenesis, and lymphangiogenesis and the expressions of VEGF-C/D were suppressed in TP KO mice. CD3ε positive cells and CD11b positive cells expressing VEGF-C/D were accumulated in diaphragm in a TP-dependent manner. These results indicated that lymphangiogenesis in diaphragm is up-regulated by TX-TP signaling via induction of VEGF-C/D, suggesting TP signaling as a potential therapeutic target.

Free Research Field

薬理学一般