Platelet activation plays a repulsive role of lymphatic to blood vessels in mouse peripheral tissues

Research Project

Project/Area Number	18K15005
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 48010:Anatomy-related
Research Institution	Niigata University (2019) Kobe University (2018)
Principal Investigator	Liu Xinyi 新潟大学, 脳研究所, 研究機関研究員 (40813928)
Project Period (FY)	2018-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	lymphatic / development / mouse / Development / Lymphatic vessel / Mouse / Platelet
Outline of Final Research Achievements	Lymphatic vessels are established as a vasculature separate from blood vessels in peripheral tissues.In this study, we analyzed Phospholipase Cγ2 (Plcg2) knockout mice, which lack platelet activation and show blood-filled lymphatic vasculature. We detected lymph-blood misconnections in embryonic back skin of Plcg2 knockout mice by fluorescent angiography, indicating the role of platelets in the maintenance of lymph-blood partitioning during lymphatic vessel elongation. We also performed time-lapse analysis and found a retraction of LEC protrusion in vitro. These effects were inhibited by an inhibitor of TGF-β signals, while TGF-β induced a retraction of LEC protrusion. In vivo analysis indicates the role of TGF-β in keeping lymphatic vessels separate from blood vessels. These results indicate a novel role for platelets in partitioning blood and lymphatic vascular compartments by promoting LEC retraction in mouse peripheral tissues.
Academic Significance and Societal Importance of the Research Achievements	We confirmed platelets function to keep lymph-blood partitioning in mouse peripheral tissues after LECs migrate out of the jugular veins. It indicate a novel role for platelets in partitioning blood and lymphatic vascular compartments by promoting LEC retraction in mouse peripheral tissues.