title: [Exendin-4 promotes paracrine action of adipose-derived stem cells through PI3K/Akt signaling pathways].
abstract: OBJECTIVE
  To investigate the mechanism by which exendin-4 promotes paracrine secretion of cytokines by adipose-derived stem cells (ADSCs).
  
  
  METHODS
  In vitro cultured SD rat ADSCs (fourth passage) with or without exendin-4 treatment underwent flow cytometry to characterize the surface markers. MTT assay was performed to assess the proliferation of the cells exposed to different concentrations (0-20 nm/L) of exendin-4, and the paracrine secretion of cytokines (bFGF, VEGF, HGF, and IGF-1) by the ADSCs was evaluated by qPCR. The changes in the expressions of p-Akt in the cells were analyzed by Western blotting and qPCR in response to exendin-4 (10 nm/L) with or without exposure to PI3K/Akt inhibitor LY-294002 (50 nm/L); bFGF, VEGF, HGF, and IGF-1 production in the cells were detected using ELISA kits.
  
  
  RESULTS
  Treatment with exendin-4 for 12 h did not affect the surface marker profile of the ADSCs but promoted the cell proliferation (P<0.05). Exendin-4 significantly increased the mRNA expressions of VEGF, bFGF, HGF, and IGF-1 in a concentration-dependent manner, and 10 nm/L was the optimum concentration (P<0.05). Exendin-4 treatment resulted in significantly increased p-Akt expressions in the ADSCs, and PI3K/Akt inhibitor not only reversed such effects of exendin-4 on p-Akt but also diminished the exendin-4- mediated up-regulation of the paracrine cytokines.
  
  
  CONCLUSIONS
  Exendin-4 can concentration-dependently promote the proliferative and paracrine capacities of ADSCs partially through the PI3K/Akt signaling pathway without affecting the surface marker profile of the cells.
authors.affiliation: Department of Cardiology, General Hospital of PLA, Beijing 100853, China.E-mail: ZHou30177@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Junjie
authors.initials: J
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Wagn
authors.forename: Shunying
authors.initials: S
authors.lastname: Hu
authors.forename: Guanghui
authors.initials: G
authors.lastname: Chen
authors.forename: Yundai
authors.initials: Y
authors.lastname: Chen
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002867:Chromones; D000077270:Exenatide; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009025:Morpholines; D010455:Peptides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology*
chemical_list: D002867:Chromones; D009025:Morpholines; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D014688:Venoms; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D000077270:Exenatide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt