|ZFIN ID: ZDB-PUB-170210-7|
Polydom Is an Extracellular Matrix Protein Involved in Lymphatic Vessel Remodeling
Morooka, N., Futaki, S., Sato-Nishiuchi, R., Nishino, M., Totani, Y., Shimono, C., Nakano, I., Nakajima, H., Mochizuki, N., Sekiguchi, K.
|Source:||Circulation research 120: 1276-1288 (Journal)|
|Registered Authors:||Mochizuki, Naoki, Nakajima, Hiroyuki|
|Keywords:||Polydom/SVEP1, embryonic development, extracellular matrix, lymphatic capillary, vascular remodeling|
|PubMed:||28179430 Full text @ Circ. Res.|
Morooka, N., Futaki, S., Sato-Nishiuchi, R., Nishino, M., Totani, Y., Shimono, C., Nakano, I., Nakajima, H., Mochizuki, N., Sekiguchi, K. (2017) Polydom Is an Extracellular Matrix Protein Involved in Lymphatic Vessel Remodeling. Circulation research. 120:1276-1288.
ABSTRACTRationale: Lymphatic vasculature constitutes a second vascular system, essential for immune surveillance and tissue fluid homeostasis. Maturation of the hierarchical vascular structure, with a highly-branched network of capillaries and ducts, is crucial for its function. Environmental cues mediate the remodeling process, but the mechanism that underlies this process is largely unknown. Objective: Polydom (also called Svep1) is an extracellular matrix protein identified as a high-affinity ligand for integrin α9β1. However, its physiological function is unclear. Here, we investigated the role of Polydom in lymphatic development.
Methods and results We generated Polydom-deficient mice. Polydom(-/-) mice showed severe edema and died immediately after birth because of respiratory failure. We found that, although a primitive lymphatic plexus was formed, it failed to undergo remodeling in Polydom(-/-) embryos, including sprouting of new capillaries and formation of collecting lymphatic vessels. Impaired lymphatic development was also observed after knockdown/knockout of polydom in zebrafish. Polydom was deposited around lymphatic vessels, but secreted from surrounding mesenchymal cells. Expression of Foxc2, a transcription factor involved in lymphatic remodeling, was decreased in Polydom(-/-) mice. Polydom bound to the lymphangiogenic factor Angiopoietin-2, which was found to upregulate Foxc2 expression in cultured lymphatic endothelial cells. Expressions of Tie1/Tie2 receptors for Angiopoietins were also decreased in Polydom(-/-) mice. Conclusions: : Polydom affects remodeling of lymphatic vessels in both mouse and zebrafish. Polydom deposited around lymphatic vessels seems to ensure Foxc2 upregulation in lymphatic endothelial cells, possibly via the Angiopoietin-2 and Tie1/Tie2 receptor system.