Involvement of Sigma Receptor-1 in Lymphatic Endothelial Barrier Integrity and Bioenergetic Regulation

Motawe, Zeinab Y.; Abdelmaboud, Salma S.; Breslin, Jerome W.

doi:10.1089/lrb.2020.0060

Cited by 6 publications

(8 citation statements)

References 49 publications

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“…As mentioned above, lymphatic barrier function or permeability plays a key role in lymphatic drainage processes. Thus, deciphering lymphatic barrier function and its regulation is crucial for understanding physiological lymphatic functions, such as lipid transport, metabolism, and immune regulation, 35–39 and the pathology of lymphatic diseases 4,27,31,40,41 . LV barrier function can be influenced by numerous factors, including extracellular matrices (ECM), 42 endothelial cell‐cell junctions, 43 endocytosis, 44 lymph flow, 45,46 lymphatic smooth muscle cell engagement, 28 and interaction with other conditions, such as inflammation 47–49 .…”

Section: Introductionmentioning

confidence: 99%

A bioengineered lymphatic vessel model for studying lymphatic endothelial cell‐cell junction and barrier function

2021

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Objective Lymphatic vessels (LVs) maintain fluid homeostasis by draining interstitial fluid. A failure in lymphatic drainage triggers lymphatic diseases such as lymphedema. Since lymphatic drainage is regulated by lymphatic barrier function, developing experimental models that assess lymphatic barrier function is critical for better understanding of lymphatic physiology and disease. Methods We built a lymphatic vessel‐on‐chip (LV‐on‐chip) by fabricating a microfluidic device that includes a hollow microchannel embedded in three‐dimensional (3D) hydrogel. Employing luminal flow in the microchannel, human lymphatic endothelial cells (LECs) seeded in the microchannel formed an engineered LV exhibiting 3D conduit structure. Results Lymphatic endothelial cells formed relatively permeable junctions in 3D collagen 1. However, adding fibronectin to the collagen 1 apparently tightened LEC junctions. We tested lymphatic barrier function by introducing dextran into LV lumens. While LECs in collagen 1 showed permeable barriers, LECs in fibronectin/collagen 1 showed reduced permeability, which was reversed by integrin α5 inhibition. Mechanistically, LECs expressed inactivated integrin α5 in collagen 1. However, integrin α5 is activated in fibronectin and enhances barrier function. Integrin α5 activation itself also tightened LEC junctions in the absence of fibronectin. Conclusions Lymphatic vessel‐on‐chip reveals integrin α5 as a regulator of lymphatic barrier function and provides a platform for studying lymphatic barrier function in various conditions.

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Section: Introductionmentioning

confidence: 99%

A bioengineered lymphatic vessel model for studying lymphatic endothelial cell‐cell junction and barrier function

2021

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“…Remarkable evidence concluded that sigma receptor-1 of the lymphatic EC is responsible for the regulation of the tone and barrier function as well as the permeability of the lymphatic tree through regulation of nitroxide biosynthesis www.acbjournal.org signaling pathway [20].…”

Section: Differences Between Lymphatic Ec and Blood Ecmentioning

confidence: 99%

Tree of life: endothelial cell in norm and disease, the good guy is a partner in crime!

Marzoog

2023

Anat Cell Biol

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Undeniably, endothelial cells (EC) contribute to the maintenance of the homeostasis of the organism through modulating cellular physiology, including signaling pathways, through the release of highly active molecules as well as the response to a myriad of extrinsic and intrinsic signaling factors. Review the data from the current literature on the EC role in norm and disease. Endothelium maintains a precise balance between the released molecules, where EC dysfunction arises when the endothelium actions shift toward vasoconstriction, the proinflammatory, prothrombic properties after the alteration of nitric oxide (NO) production and oxidative stress. The functions of the EC are regulated by the negative/ positive feedback from the organism, through EC surface receptors, and the crosstalk between NO, adrenergic receptors, and oxidative stress. More than a hundred substances can interact with EC. The EC dysfunction is a hallmark in the emergence and progression of vascular-related pathologies. The paper concisely reviews recent advances in EC (patho) physiology. Grasping EC physiology is crucial to gauge their potential clinical utility and optimize the current therapies as well as to establish novel nanotherapeutic molecular targets include; endothelial receptors, cell adhesion molecules, integrins, signaling pathways, enzymes; peptidases.

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Section: Types Of Endothelial Cellsmentioning

confidence: 99%

Endothelial cell autophagy in the context of disease development

Marzoog

2022

Anat Cell Biol

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Endothelial cells (EC) are the anatomical boundaries between the intravascular and extravascular space. Damage to ECs is catastrophic and induces endothelial cell dysfunction. The pathogenesis is multifactorial and involves dysregulation in the signaling pathways, membrane lipids ratio disturbance, cell-cell adhesion disturbance, unfolded protein response, lysosomal and mitochondrial stress, autophagy dysregulation, and oxidative stress. Autophagy is a lysosomal-dependent turnover of intracellular components. Autophagy was recognized early in the pathogenesis of endothelial dysfunction. Autophagy is a remarkable patho (physiological) process in the cell homeostasis regulation including EC. Regulation of autophagy rate is disease-dependent and impaired with aging. Up-regulation of autophagy induces endothelial cell regeneration/differentiation and improves the function of impaired ones. The paper scrutinizes the molecular mechanisms and triggers of EC dysregulation and current perspectives for future therapeutic strategies by autophagy targeting.

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Involvement of Sigma Receptor-1 in Lymphatic Endothelial Barrier Integrity and Bioenergetic Regulation

Cited by 6 publications

References 49 publications

A bioengineered lymphatic vessel model for studying lymphatic endothelial cell‐cell junction and barrier function

A bioengineered lymphatic vessel model for studying lymphatic endothelial cell‐cell junction and barrier function

Tree of life: endothelial cell in norm and disease, the good guy is a partner in crime!

Endothelial cell autophagy in the context of disease development

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