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

2019 Fiscal Year Annual Research Report

• Project/Area Number: 18K15005
• Research Institution: Niigata University
• Principal Investigator: 劉 シンイ 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
• Keywords: lymphatic / development / mouse

Outline of Annual Research Achievements

Platelets are critical in the separation process by forming aggregates around the opening of lymph sacs derived from the jugular vein during the initial phase of lymphatic vessel development. How platelets keep lymphatic vessels separate from blood vessels during lymphatic sprouting remains unknown. In this study, I analyzed Phospholipase Cγ2 knockout mice, which lack platelet activation and show blood-filled lymphatic vasculature. I 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. In vitro analysis showed that platelets or activated platelet-conditioned medium inhibits LEC migration and proliferation in a Syk- or Plcg-dependent manner. To investigate an immediate response of LECs to platelets or activated platelet-conditioned medium, I performed time-lapse analysis and found a retraction of LEC protrusion. 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.