Molecular Mechanisms Controlling Lymphatic Endothelial Junction Integrity.
Molecular Mechanisms Controlling Lymphatic Endothelial Junction Integrity.
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DOI：
10.3389/fcell.2020.627647
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发表时间：
2020
影响因子：
5.5
通讯作者：
Kume T
中科院分区：
文献类型：
--
作者：
Norden PR;Kume T
淋巴系统对于消化系统的脂质吸收/运输、组织液和蛋白质稳态的维持以及免疫监视至关重要。尽管最近在理解淋巴管系统形成的细胞和分子机制方面取得了进展，但人类淋巴管异常和疾病的本质是复杂的且知之甚少。成熟的淋巴管系统形成一个分层网络，其中淋巴内皮细胞（LEC）通过功能特化的细胞-细胞连接点连接起来，以维持淋巴管的完整性。盲端和高渗透性的毛细淋巴管通过不连续的、纽扣状的LEC连接排出间质液，而收集淋巴管被完整的基底膜和淋巴平滑肌细胞包围，具有连续的、拉链状的LEC连接，将淋巴液输送到血液循环系统而不渗漏。在这篇综述中，我们讨论了我们对淋巴纽扣样和拉链样连接在组织和器官特异性方式的淋巴通透性和功能中发挥关键作用的机制的最新进展，包括小肠的乳糜管。我们还提供与控制淋巴内皮细胞连接完整性的 VEGF 和 RhoA/ROCK 信号等关键通路和因子相关的最新知识。
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.
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