title: Mesenchymal Stem Cells Alleviate LPS-Induced Acute Lung Injury in Mice by MiR-142a-5p-Controlled Pulmonary Endothelial Cell Autophagy.
abstract: OBJECTIVE
  Damages of pulmonary endothelial cells (PECs) represent a critical pathological process during acute lung injury (ALI), and precede pulmonary epithelial cell injury, and long-term lung dysfunction. Transplantation of mesenchymal stem cells (MSCs) has proven therapeutic effects on ALI, whereas the underlying mechanisms remain ill-defined.
  
  
  METHODS
  We transplanted MSCs in mice and then induced ALI using Lipopolysaccharides (LPS). We analyzed the changes in permeability index and lung histology. Mouse PECs were isolated by flow cytometry based on CD31 expression and then analyzed for autophagy-associated factors LC3 and Beclin-1 by Western blot. Beclin-1 mRNA was determined by RT-qPCR. In vitro, we performed bioinformatics analyses to identify the MSCs-regulated miRNAs that target Beclin-1, and confirmed that the binding was functional by 3'-UTR luciferase reporter assay.
  
  
  RESULTS
  We found that MSCs transplantation significantly reduced the severity of LPS-induced ALI in mice. MSCs increased autophagy of PECs to promote PEC survival. MSCs increased Beclin-1 protein but not mRNA. MiR-142a-5p was found to target the 3'-UTR of Beclin-1 mRNA to inhibit its protein translation in PECs. MSCs reduced the levels of miR-142a-5p in PECs from LPS-treated mice.
  
  
  CONCLUSIONS
  MSCs may alleviate LPS-ALI through downregulation of miR-142a-5p, which allows PECs to increase Beclin-1-mediated cell autophagy.
authors.affiliation: Department of Anesthesiology, Taizhou Hospital of Traditional Chinese Medicine, Taizhou, China.
authors.forename: Zichao
authors.initials: Z
authors.lastname: Zhou
authors.forename: Zhijian
authors.initials: Z
authors.lastname: You
mesh_terms: D020413:3' Untranslated Regions; D055371:Acute Lung Injury / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D001483:Base Sequence; D000071186:Beclin-1; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D008070:Lipopolysaccharides; C480860:Map1lc3b protein, mouse; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D016376:Oligonucleotides, Antisense; D019408:Platelet Endothelial Cell Adhesion Molecule-1