scholarly journals Sphingosine 1-Phosphate Receptor Signaling Establishes AP-1 Gradients to Allow for Retinal Endothelial Cell Specialization

2020 ◽  
Vol 52 (6) ◽  
pp. 779-793.e7 ◽  
Author(s):  
Keisuke Yanagida ◽  
Eric Engelbrecht ◽  
Colin Niaudet ◽  
Bongnam Jung ◽  
Konstantin Gaengel ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Receptor Signaling ◽  
Sphingosine 1 Phosphate ◽  
Retinal Endothelial Cell ◽  
Cell Specialization

Abstract 13667: Programming to S1PR1 + Endothelial Cell Population Promotes the Restoration of Vascular Integrity in vivo

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Zahid Akhter ◽  
Jagdish Chandra Joshi ◽  
Vijay Avin Balaji Ragunathrao ◽  
Richard L Proia ◽  
Asrar B Malik ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Lung Injury ◽  
Endothelial Permeability ◽  
Vascular Diseases ◽  
Mechanistic Study ◽  
Rna Seq ◽  
Vascular Integrity ◽  
Injured Lung ◽  
Sphingosine 1 Phosphate

Introduction: Increased endothelial permeability and failure to repair is the hallmark of several vascular diseases including acute lung injury (ALI). However, little is known about the intrinsic pathways that activate the endothelial cell (EC) regenerative programs facilitating thereby tissue repair. Studies have invoked a crucial role of sphingosine-1-phosphate (S1P) in resolving endothelial hyperpermeability through activation of the G-protein coupled receptor, sphingosine-1-phosphate receptor 1 (S1PR1). Hypothesis: We postulate that S1PR1 + EC serve as an endogenous means to prevent endothelial injury. Methods: Studies were made using EC-S1PR1 null mice and S1PR1-GFP reporter mice to trace the generation and characteristics of S1PR1 + EC by exploiting immuno-histochemical analysis and FACS. RNA-seq analysis was performed to identify the genetic signature of S1PR1 + EC. Combination of genetic and pharmacological strategies were included for mechanistic study. Transplantation of S1PR1 + EC and edema measurement was performed in EC-S1PR1 null mice. Results: We observed in a mouse model of endotoxemia that LPS via generation of S1P induced the programming of S1PR1 lo EC to S1PR1 + EC, comprising 80% of lung EC. Their generation preceded the vascular repair phase and these cells were required for reestablishing the endothelial barrier function. Thus, conditional deletion of S1PR1 in EC spontaneously increased lung vascular permeability. RNA-seq analysis of S1PR1 + EC showed enrichment of genes regulating S1P synthesis and transport, sphingosine kinase 1 (SPHK1) and SPNS2, respectively, as well as transcription factors EGR1 and STAT3. EGR1 and STAT3 were essential for transcribing SPHK1 and SPNS2, respectively to increase S1P concentration that served to amplify S1PR1 + EC transition. Transplantation of S1PR1 + EC into injured lung vasculature of EC-S1PR1 -/- mice restored endothelial integrity. Conclusions: Findings illustrate that generation of a specialized S1PR1 + EC population has the potential to activate key endothelial regenerative program mediating vascular endothelial repair raising the possibility of activating this pathway to restore vascular homeostasis in inflammatory lung injury.

scholarly journals TNFα and SOCS3 regulate IRS-1 to increase retinal endothelial cell apoptosis

2012 ◽  
Vol 24 (5) ◽  
pp. 1086-1092 ◽  
Author(s):  
Youde Jiang ◽  
Qiuhua Zhang ◽  
Carl Soderland ◽  
Jena J. Steinle
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Endothelial Cell Apoptosis ◽  
Retinal Endothelial Cell

scholarly journals SIRT1 Deletion Impairs Retinal Endothelial Cell Migration Through Downregulation of VEGF-A/VEGFR-2 and MMP14

2018 ◽  
Vol 59 (13) ◽  
pp. 5431 ◽  
Author(s):  
Yong Lin ◽  
Li Li ◽  
Junjie Liu ◽  
Xiaoting Zhao ◽  
Juxiu Ye ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Endothelial Cell Migration ◽  
Retinal Endothelial Cell

scholarly journals S1P/S1P Receptor Signaling in Neuromuscolar Disorders

2019 ◽  
Vol 20 (24) ◽  
pp. 6364 ◽  
Author(s):  
Elisabetta Meacci ◽  
Mercedes Garcia-Gil
Keyword(s):  
Neuromuscular Diseases ◽  
Clinical Applications ◽  
G Protein Coupled Receptors ◽  
Receptor Signaling ◽  
Charcot Marie Tooth Disease ◽  
System Degeneration ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
G Protein Coupled ◽  
Tooth Disease

The bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P), and the signaling pathways triggered by its binding to specific G protein-coupled receptors play a critical regulatory role in many pathophysiological processes, including skeletal muscle and nervous system degeneration. The signaling transduced by S1P binding appears to be much more complex than previously thought, with important implications for clinical applications and for personalized medicine. In particular, the understanding of S1P/S1P receptor signaling functions in specific compartmentalized locations of the cell is worthy of being better investigated, because in various circumstances it might be crucial for the development or/and the progression of neuromuscular diseases, such as Charcot–Marie–Tooth disease, myasthenia gravis, and Duchenne muscular dystrophy.

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