Lymphatic vascular development and related diseases

 

Masanori Hirashima

Professor, Division of Pharmacology

Graduate School of Medicine, Dentistry and Health Sciences, Niigata University

 

Lymphatic vessels, together with blood vessels, form the body’s lifeline and play a vital role in maintaining fluid homeostasis, immune responses, lipid absorption and the removal of foreign substances. During development, lymphatic endothelial cells differentiate from venous endothelial cells to form lymph sacs, which fuse with one another to form the lymphatic network. In adults, the lymphatic network is separated from the vascular network in peripheral tissues, but it anastomoses with blood vessels near the venous angle in the neck, returning lymph collected from throughout the body to the veins. Abnormalities in the developmental process are closely linked to the development of pathological conditions and are responsible for conditions such as fetal nuchal edema and lymphatic malformations (lymphangiomas). Furthermore, if there are abnormalities in platelet activation triggered by contact with lymphatic endothelial cells, the lymphatic and vascular systems fail to separate correctly. In this seminar, focusing on these topics elucidated through the analysis of mouse models, I will introduce the molecular mechanisms of lymphangiogenesis and the pathologies arising from their abnormalities, and discuss the potential for vascular regulation based on these findings.

 

Reference

Osada M, Inoue O, Ding G, Shirai T, Ichise H, Hirayama K, Takano K, Yatomi Y, Hirashima M, Fujii H, Suzuki-Inoue K, Ozaki Y. Platelet activation receptor CLEC-2 regulates blood/lymphatic vessel separation by inhibiting proliferation, migration, and tube formation of lymphatic endothelial cells. J Biol Chem 287(26):22241-22252, 2012

Otowa Y, Moriwaki K, Sano K, Shirakabe M, Yonemura S, Shibuya M, Rossant J, Suda T, Kakeji Y, Hirashima M. Flt1/VEGFR1 heterozygosity causes transient embryonic edema. Sci Rep 6:27186, 2016

Sugiyama A, Hirashima M. Fetal nuchal edema and developmental anomalies caused by gene mutations in mice. Front Cell Dev Biol 10:949013, 2022