Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress

Surya, Vinay N.; Michalaki, Eleftheria; Huang, Eva Y.; Fuller, Gerald G.; Dunn, Alexander R.

doi:10.1098/rsif.2016.0823

Cited by 15 publications

(13 citation statements)

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“…4). We have previously observed that HLMVECs migrate against the direction of flow 24,30,31 . Here, we observed that, in the presence of flow, HLMVECs moved towards the constriction site (x-direction) but did not show migration in the direction of flow (y-direction) ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 97%

“…Determination of cell migration: brightfield movies were processed in the same way as our previous publications 24,30 . Movies were processed with Fiji software and analyzed using custom Matlab routines.…”

Section: Methodsmentioning

confidence: 99%

“…These studies and others identified PECAM-1, VE-cadherin, VEGFR-2 and VEGFR-3 as components of a signaling pathway that converts the physical stimulus provided by WSS into downstream signaling via VEGFR and PI3K signaling 16,[19][20][21] . G-protein-coupled receptors (GPCRs), such as bradykinin B2 22 and sphingosine 1-phosphate receptor 1 (S1PR1), have also been implicated in the response of ECs to fluid flow 23,24 . Despite these and other studies, how exactly ECs, and LECs specifically, may sense spatial variations in WSS remains little examined, due in part to a lack of experimental tools for exposing (L)ECs to controlled gradients in WSS.…”

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confidence: 99%

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Perpendicular alignment of lymphatic endothelial cells in response to spatial gradients in wall shear stress

et al. 2020

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One-way valves in the lymphatic system form from lymphatic endothelial cells (LECs) during embryonic development and are required for efficient tissue drainage. Although fluid flow is thought to guide both valve formation and maintenance, how this occurs at a mechanistic level remains incompletely understood. We built microfluidic devices that reproduce critical aspects of the fluid flow patterns found at sites of valvulogenesis. Using these devices, we observed that LECs replicated aspects of the early steps in valvulogenesis: cells oriented perpendicular to flow in the region of maximum wall shear stress (WSS) and exhibited enhanced nuclear localization of FOXC2, a transcription factor required for valvulogenesis. Further experiments revealed that the cell surface protein E-selectin was required for both of these responses. Our observations suggest that spatial gradients in WSS help to demarcate the locations of valve formation, and implicate E-selectin as a component of a mechanosensory process for detecting WSS gradients.

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Section: Resultsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Perpendicular alignment of lymphatic endothelial cells in response to spatial gradients in wall shear stress

et al. 2020

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“…However, these same cells at lower density exhibited the opposite behavior by moving with the direction of flow. Using a similar in vitro system, Surya et al demonstrated that S1P signaling is involved with the collective migration of LECs.…”

Section: Lymphatic Vessel Physiology Function and Lymphangiogenesismentioning

confidence: 99%

Application of microscale culture technologies for studying lymphatic vessel biology

2019

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Immense progress in microscale engineering technologies has significantly expanded the capabilities of in vitro cell culture systems for reconstituting physiological microenvironments that are mediated by biomolecular gradients, fluid transport, and mechanical forces. Here, we examine the innovative approaches based on microfabricated vessels for studying lymphatic biology. To help understand the necessary design requirements for microfluidic models, we first summarize lymphatic vessel structure and function. Next, we provide an overview of the molecular and biomechanical mediators of lymphatic vessel function. Then we discuss the past achievements and new opportunities for microfluidic culture models to a broad range of applications pertaining to lymphatic vessel physiology. We emphasize the unique attributes of microfluidic systems that enable the recapitulation of multiple physicochemical cues in vitro for studying lymphatic pathophysiology. Current challenges and future outlooks of microscale technology for studying lymphatics are also discussed. Collectively, we make the assertion that further progress in the development of microscale models will continue to enrich our mechanistic understanding of lymphatic biology and physiology to help realize the promise of the lymphatic vasculature as a therapeutic target for a broad spectrum of diseases.

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“…In areas of laminar flow with high shear stress, S1P1 is present on the membrane, whereas it is internalized in areas of disturbed flow with low shear stress. S1P1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress, which is required plasma or S1P [77]. The change in S1P1 might associate with remodeling of the glycocalyx.…”

Section: New Insights On Endothelial Glycocalyx and Atherosclerosismentioning

confidence: 99%

Endothelial Glycocalyx: Novel Insight into Atherosclerosis

Zeng¹

2017

J. Biomed

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The evidence shows that endothelial glycocalyx exerts an important role in inflammation and atherosclerosis. We previously demonstrated that hydrodynamic force such as shear stress induces the remodeling of the major component of glycocalyx including glypican-1 with attached heparan sulfate, and that sphingosine-1-phosphate (S1P) protects the glycocalyx against syndecan-1 ectodomain shedding and induces the synthesis of HS. Actually, both shear stress and S1P imposed significant influence on inflammatory disease such as atherosclerosis. Therefore, it can be concluded that glycocalyx is a critical signaling platform for determining the fate of endothelial cells and atherosclerosis. This review integrated our current understanding of shear stress, S1P and glycocalyx, and also provided new insight/issues into the role of the glycocalyx in the process of forming and developing atherosclerosis.

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Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress

Cited by 15 publications

References 59 publications

Perpendicular alignment of lymphatic endothelial cells in response to spatial gradients in wall shear stress

Perpendicular alignment of lymphatic endothelial cells in response to spatial gradients in wall shear stress

Application of microscale culture technologies for studying lymphatic vessel biology

Endothelial Glycocalyx: Novel Insight into Atherosclerosis

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