Polydom Is an Extracellular Matrix Protein Involved in Lymphatic Vessel Remodeling
| Autor: | Itsuko Nakano, Naoki Mochizuki, Hiroyuki Nakajima, Ryoko Sato-Nishiuchi, Chisei Shimono, Yuta Totani, Sugiko Futaki, Kiyotoshi Sekiguchi, Masafumi Nishino, Nanami Morooka |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty biology Physiology government.form_of_government Lymphatic plexus Lymphatic Capillary TIE1 Cell biology 03 medical and health sciences Lymphatic Endothelium 030104 developmental biology 0302 clinical medicine Lymphatic system medicine.anatomical_structure medicine biology.protein Lymphatic vessel government Lymph sacs Cardiology and Cardiovascular Medicine FOXC2 030217 neurology & neurosurgery |
| Zdroj: | Circulation Research. 120:1276-1288 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/circresaha.116.308825 |
| Popis: | Rationale: 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 (forkhead box protein c2), a transcription factor involved in lymphatic remodeling, was decreased in Polydom −/− mice. Polydom bound to the lymphangiogenic factor Ang-2 (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 Ang-2 and Tie1/Tie2 receptor system. |
| Databáze: | OpenAIRE |
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