Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration

Polzin, Amin; Knoop, Betül; Böhm, Andreas; Dannenberg, Lisa; Zurek, Mark; Zeus, Tobias; Kelm, Malte; Levkau, Bodo; Rauch, Bernhard

doi:10.1159/000484208

Cited by 4 publications

(4 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S1P is a bioactive sphingolipid metabolite involved in regulating diverse cellular process by binding to a family of five specific G protein-coupled receptors (S1PR 1-5 ), which are present in most tissues but heterogeneous in their expression (2,42,55). It has been shown that S1P is elevated in the airways of individuals with asthma and stimulates ASMC proliferation, migration, and contraction in vitro (1,18,45).…”

Section: Discussionmentioning

confidence: 99%

Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating Hippo signaling effector YAP

Liu

Zhai

Pan

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Sphingosine-1-phosphate (S1P), a bioactive lipid, has been shown to be elevated in the airways of individuals with asthma and modulates the airway smooth muscle cell (ASMC) functions, yet its underlying molecular mechanisms are not completely understood. The aim of the present study is to address this issue. S1P induced yes-associated protein (YAP) dephosphorylation and nuclear localization via the S1PR/Rho-associated protein kinase (ROCK) pathway, and this in turn increased forkhead box M1 (FOXM1) and cyclin D1 expression leading to ASMC proliferation, migration, and contraction. Pretreatment of cells with S1PR antagonist JTE013, S1PR antagonist CAY10444, or ROCK inhibitor Y27632 blocked S1P-induced alterations of YAP, FOXM1, cyclin D1, and ASMC proliferation, migration, and contraction. In addition, prior silencing of YAP or FOXM1 with siRNA reversed the effect of S1P on ASMC functions. Taken together, our study indicates that S1P stimulates ASMC proliferation, migration, and contraction by binding to S1PR and modulating ROCK/YAP/FOXM1 axis and suggests that targeting this pathway might have potential value in the management of asthma.

show abstract

Section: Discussionmentioning

confidence: 99%

Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating Hippo signaling effector YAP

Liu

Zhai

Pan

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…222 Further exploration has revealed that S1P induces endothelial-cell migration in a concentration-dependent manner, and S1PR1 inhibition abrogates the endothelial-cell migration induced by activated platelets; suppression of S1PR2 or S1PR3 does not induce this effect. 223 Similarly, an indepth assessment of S1P concentration and S1PR expression needs to be performed. SPNS2, a major transporter of S1P in endothelial cells, mediates extracellular pathways of S1P and S1PRs, and influences endothelial-cell migration and angiogenesis.…”

Section: Endothelial Cellsmentioning

confidence: 99%

“…Additionally, hypoxia can enhance the interaction between exogenous S1P and S1PR1 and promote the migration of endothelial cells 222 . Further exploration has revealed that S1P induces endothelial‐cell migration in a concentration‐dependent manner, and S1PR1 inhibition abrogates the endothelial‐cell migration induced by activated platelets; suppression of S1PR2 or S1PR3 does not induce this effect 223 . Similarly, an in‐depth assessment of S1P concentration and S1PR expression needs to be performed.…”

Section: The Role Of the S1p Axis In Metabolic‐related Diseasesmentioning

confidence: 99%

Sphingosine‐1‐phosphate in mitochondrial function and metabolic diseases

et al. 2022

View full text Add to dashboard Cite

Summary Sphingosine‐1‐phosphate (S1P) is a bioactive sphingolipid metabolite. The past decade has witnessed exponential growth in the field of S1P research, partly attributed to drugs targeting its receptors or kinases. Accumulating evidence indicates that changes in the S1P axis (i.e., S1P production, transport, and receptors) may modify metabolism and eventually mediate metabolic diseases. Dysfunction of the mitochondria on a master monitor of cellular metabolism is considered the leading cause of metabolic diseases, with aberrations typically induced by abnormal biogenesis, respiratory chain complex disorders, reactive oxygen species overproduction, calcium deposition, and mitophagy impairment. Accordingly, we discuss decades of investigation into changes in the S1P axis and how it controls mitochondrial function. Furthermore, we summarize recent scientific advances in disorders associated with the S1P axis and their involvement in the pathogenesis of metabolic diseases in humans, including type 2 diabetes mellitus and cardiovascular disease, from the perspective of mitochondrial function. Finally, we review potential challenges and prospects for S1P axis application to the regulation of mitochondrial function and metabolic diseases; these data may provide theoretical guidance for the treatment of metabolic diseases.

show abstract

“…Erythrocytes and endothelial cells seem to be the main sources of S1P in plasma; however, platelets also express abundant amounts of S1P [32], and during inflammation and vascular damage, platelets become activated and locally release high levels of S1P [32]. It is noteworthy that these platelet-mediated endothelial protective processes are inhibited by aspirin and NSAIDs, often used to relieve symptoms of infections [33][34][35][36]. Especially worrisome in this regard is the fact that the increase in T1D incidence is paralleled by the increased use of these medications and the observation that the use of NSAIDs is especially frequent in countries with a high incidence of T1D, such as Sweden and Finland [37][38][39].…”

Section: The Vascular Bed Of the Islets As A Hereto-neglected "Locus mentioning

confidence: 99%

On the dynamics of the human endocrine pancreas and potential consequences for the development of type 1 diabetes

Skog

Korsgren

2019

Acta Diabetol

View full text Add to dashboard Cite

Little is known about the human islet life span, and beta-cell neogenesis is generally considered rare in adults. However, based on available data on beta-cell proliferation, calculations can be made suggesting that the dynamics of the endocrine pancreas is considerable even during adulthood, with islet neogenesis and a sustained increase in size of already formed islets. Islet-associated hemorrhages, frequently observed in most mammals including humans, could account for a considerable loss of islet parenchyma balancing the constant beta-cell proliferation. Notably, in subjects with type 1 diabetes, periductal accumulation of leukocytes and fibrosis is frequently observed, findings that are likely to negatively affect islet neogenesis from endocrine progenitor cells present in the periductal area. Impaired neogenesis would disrupt the balance, result in loss of islet mass, and eventually lead to beta-cell deficiency and compromised glucose metabolism, with increased islet workload and blood perfusion of remaining islets. These changes would impose initiation of a vicious circle further increasing the frequency of vascular events and hemorrhages within remaining islets until the patient eventually loses all beta-cells and becomes c-peptide negative.

show abstract

Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration

Cited by 4 publications

References 13 publications

Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating Hippo signaling effector YAP

Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating Hippo signaling effector YAP

Sphingosine‐1‐phosphate in mitochondrial function and metabolic diseases

On the dynamics of the human endocrine pancreas and potential consequences for the development of type 1 diabetes

Contact Info

Product

Resources

About