title: Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury.
abstract: BACKGROUND
  Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30-40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs) exhibit make it possible to regulate the homeostatic control of S1P.
  
  
  METHODS
  By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis.
  
  
  RESULTS
  It was found that the down-regulation of TNF-αexpression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes.
  
  
  CONCLUSIONS
  The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1P and their possible synergistic mechanism.
authors.affiliation: Department of Respiratory and Critical Care Diseases, 307th Hospital of PLA , Beijing , The People's Republic of China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Diseases, 307th Hospital of PLA , Beijing , The People's Republic of China.
authors.forename: Zili
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Respiratory and Critical Care Diseases, 307th Hospital of PLA , Beijing , The People's Republic of China.
authors.forename: Puyuan
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Diseases, 307th Hospital of PLA , Beijing , The People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Respiratory and Critical Care Diseases, 307th Hospital of PLA , Beijing , The People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Beijing Oriental Yamei Gene Science & Technology Institute , Beijing , The People's Republic of China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Diseases, 307th Hospital of PLA , Beijing , The People's Republic of China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Bai
authors.affiliation: Department of Respiratory and Critical Care Diseases, 307th Hospital of PLA , Beijing , The People's Republic of China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Niu
keywords: Acute pulmonary endothelial cell injury; Mesenchymal stem cells; S1p receptors; Sphingosine-1-phosphate