title: High density lipoprotein promotes proliferation of adipose-derived stem cells via S1P1 receptor and Akt, ERK1/2 signal pathways.
abstract: BACKGROUND
  Adipose-derived stem cells (ADSC) are non-hematopoietic mesenchymal stem cells that have shown great promise in their ability to differentiate into multiple cell lineages. Their ubiquitous nature and the ease of harvesting have attracted the attention of many researchers, and they pose as an ideal candidate for applications in regenerative medicine. Several reports have demonstrated that transplanting ADSC can promote repair of injured tissue and angiogenesis in animal models. Survival of these cells after transplant remains a key limiting factor for the success of ADSC transplantation. Circulating factors like High Density Lipoprotein (HDL) has been known to promote survival of other stems cells like bone marrow derived stem cells and endothelial progenitor cells, both by proliferation and by inhibiting cell apoptosis. The effect of HDL on transplanted adipose-derived stem cells in vivo is largely unknown.
  
  
  METHODS
  This study focused on exploring the effects of plasma HDL on ADSC and delineating the mechanisms involved in their proliferation after entering the bloodstream. Using the MTT and BrdU assays, we tested the effects of HDL on ADSC proliferation. We probed the downstream intracellular Akt and ERK1/2 signaling pathways and expression of cyclin proteins in ADSC using western blot.
  
  
  RESULTS
  Our study found that HDL promotes proliferation of ADSC, by binding to sphingosine-1- phosphate receptor-1(S1P1) on the cell membrane. This interaction led to activation of intracellular Akt and ERK1/2 signaling pathways, resulting in increased expression of cyclin D1 and cyclin E, and simultaneous reduction in expression of cyclin-dependent kinase inhibitors p21 and p27, therefore promoting cell cycle progression and cell proliferation.
  
  
  CONCLUSIONS
  These studies raise the possibility that HDL may be a physiologic regulator of stem cells and increasing HDL concentrations may be valuable strategy to promote ADSC transplantation.
authors.affiliation: Department of Pathology, Shantou University Medical College, Shantou, Guangdong, 515041, China. dagezi120@126.com.|Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China. dagezi120@126.com.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Peking University Health Science Center, Beijing, 100191, China. zhouenchen@126.com.
authors.forename: Enchen
authors.initials: E
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Shantou University Medical College, Shantou, Guangdong, 515041, China. weixiujingcpu@126.com.|Hutchison Medi Pharma (Suzhou), Jiangsu, 215125, China. weixiujingcpu@126.com.
authors.forename: Xiujing
authors.initials: X
authors.lastname: Wei
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Peking University Health Science Center, Beijing, 100191, China. fzwluck12@163.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Fu
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Peking University Health Science Center, Beijing, 100191, China. asdncg@pku.edu.cn.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Niu
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Peking University Health Science Center, Beijing, 100191, China. liyang@bjmu.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Peking University Health Science Center, Beijing, 100191, China. panbintz@163.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Pan
authors.affiliation: Department of Medicine, University of Michigan, Ann Arbor, MI, 48109, USA. amat@med.umich.edu.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Mathew
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Peking University Health Science Center, Beijing, 100191, China. wangxu199197@163.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of Michigan, Ann Arbor, MI, 48109, USA. spennath@med.umich.edu.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Peking University Health Science Center, Beijing, 100191, China. zhengl@bjmu.edu.cn.
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Institute of Hypoxia Medicine, Wenzhou Medical University, Zhejiang, 325035, China. yywangut@gmail.com.
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D002867:Chromones; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008075:Lipoproteins, HDL; D009025:Morpholines; D049349:Receptors, Lysosphingolipid; D050760:Cyclin-Dependent Kinase Inhibitor p27; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3