title: Mesenchymal Stem Cell Conditioned Medium Promotes Proliferation and Migration of Alveolar Epithelial Cells under Septic Conditions In Vitro via the JNK-P38 Signaling Pathway.
abstract: OBJECTIVE
  Mesenchymal stem cell (MSC) based therapies may be useful for treating acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC) secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways.
  
  
  METHODS
  Human alveolar epithelial cells (AEC) and primary human small airway epithelial cells (SAEC) were subjected to lipopolysaccharide (LPS) with or without the presence of hUC-MSC-conditioned medium (CM). Proliferation and migration of AEC and SAEC were determined via an MTT assay, a wound healing assay and a transwell migration assay (only for AEC). Protein phosphorylation was determined by western blot and the experiments were repeated in presence of small-molecule inhibitors. The hMSC-secretory proteins were identified by LC-MS/MS mass spectrometry.
  
  
  RESULTS
  MSC-CM enhanced proliferation and migration. Activation of JNK and P38, but not ERK, was required for the proliferation and migration of AEC and SAEC. Pretreatment of AEC or SAEC with SP600125, an inhibitor of JNK1 or SB200358, an inhibitor of P38, significantly reduced cell proliferation and migration. An array of proteins including TGF-beta receptor type-1, TGF-beta receptor type-2, Ras-related C3 botulinum toxin substrate 1 and Ras-related C3 botulinum toxin substrate 2 which influencing the proliferation and migration of AEC and SAEC were detected in MSC-CM.
  
  
  CONCLUSIONS
  Our data suggest MSC promote epithelial cell repair through releasing a repertoire of paracrine factors via activation of JNK and P38 MAPK.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Li
authors.forename: Haojie
authors.initials: H
authors.lastname: Hao
authors.forename: Chonghui
authors.initials: C
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Du
authors.forename: Ye
authors.initials: Y
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Liang
authors.forename: Chunsun
authors.initials: C
authors.lastname: Li
authors.forename: Jiejie
authors.initials: J
authors.lastname: Liu
authors.forename: Liangan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D014470:Umbilical Cord / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D054852:Small Molecule Libraries; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases