Molecular Mechanisms Controlling Lymphatic Endothelial Junction Integrity
Open Access
- 14 January 2021
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
The lymphatic system is essential for lipid absorption/transport from the digestive system, maintenance of tissue fluid and protein homeostasis, and immune surveillance. Despite recent progress toward understanding the cellular and molecular mechanisms underlying the formation of the lymphatic vascular system, the nature of lymphatic vessel abnormalities and disease in humans is complex and poorly understood. The mature lymphatic vasculature forms a hierarchical network in which lymphatic endothelial cells (LECs) are joined by functionally specialized cell-cell junctions to maintain the integrity of lymphatic vessels. Blind-ended and highly permeable lymphatic capillaries drain interstitial fluid via discontinuous, button-like LEC junctions, whereas collecting lymphatic vessels, surrounded by intact basement membranes and lymphatic smooth muscle cells, have continuous, zipper-like LEC junctions to transport lymph to the blood circulatory system without leakage. In this review, we discuss the recent advances in our understanding of the mechanisms by which lymphatic button- and zipper-like junctions play critical roles in lymphatic permeability and function in a tissue- and organ-specific manner, including lacteals of the small intestine. We also provide current knowledge related to key pathways and factors such as VEGF and RhoA/ROCK signaling that control lymphatic endothelial cell junctional integrity.Keywords
This publication has 105 references indexed in Scilit:
- A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopyThe EMBO Journal, 2013
- Plasticity of Button-Like Junctions in the Endothelium of Airway Lymphatics in Development and InflammationThe American Journal of Pathology, 2012
- SnapShot: Bioactive LysophospholipidsCell, 2012
- A genetically encoded photoactivatable Rac controls the motility of living cellsNature, 2009
- Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutationsEuropean Journal of Human Genetics, 2009
- A tissue‐engineered model of the intestinal lacteal for evaluating lipid transport by lymphaticsBiotechnology & Bioengineering, 2009
- Transcriptional Control of Endothelial Cell DevelopmentDevelopmental Cell, 2009
- The Control of Vascular Integrity by Endothelial Cell Junctions: Molecular Basis and Pathological ImplicationsDevelopmental Cell, 2009
- Organization and signaling of endothelial cell-to-cell junctions in various regions of the blood and lymphatic vascular treesCell and tissue research, 2008
- Defective remodeling and maturation of the lymphatic vasculature in Angiopoietin-2 deficient miceDevelopmental Biology, 2008