title: Effects of bone marrow MSCs transfected with sRAGE on the intervention of HMGB1 induced immuno-inflammatory reaction.
abstract: BACKGROUND
  High mobility group box chromosomal protein 1 (HMGB1) is an important proinflammatory molecule in many inflammatory disorders, but little is known about its role in acute liver failure (ALF). In this study, we determined the plasma and hepatic tissue levels of HMGB1 in a d-galactosamine-induced rat ALF model and investigated the effect of soluble receptor for advanced glycation end products (sRAGE) on ALF successfully.
  
  
  METHODS
  Male Sprague-Dawley rats were divided into five groups randomly. Group A (Control group, n=20) received administrated saline via peritoneal cavity. Group B (ALF group, n=20) induced by d-galactosamine (0.6 g/kg) via peritoneal cavity. Group C (HMGB1 group, n=20) were treated with HMGB1 recombination protein (200 μg/kg) via penile vein after ALF model induced. Group D (sRAGE group, n=20) received administrated sRAGE recombination protein (400 μg/kg) via penile vein after ALF model induced. Group E (sRAGE-MSC group, n=20) received 3 × 10(6) MSC transplantation which could maintain a stable expression of sRAGE via penile vein after ALF model induced. Liver function, level of cytokines and liver pathological changes were measured.
  
  
  RESULTS
  We determined that the plasma levels and hepatic tissue levels of HMGB1 were significant increased in ALF model (P<0.05). SRAGE group and sRAGE-MSC group could significantly prolong ALF rat survival time, as well as improve its liver functions, inflammatory cytokines level and hepatocytes necrosis.
  
  
  CONCLUSIONS
  SRAGE as a ligand decoy has illustrated largely beneficial effects on reducing immuno-inflammatory response, which holds promise for the identification of potential therapeutic targets and/or biomarkers of RAGE activity in ALF.
authors.affiliation: Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College of Nanjing Medical University Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing, China ; Jiangsu Province's Key Medical Center for Digestive Disease Nanjing, China ; Institute of Hepatobiliary Surgery, Nanjing University Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Drum Tower Clinical Medical College of Nanjing Medical University Nanjing, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College of Nanjing Medical University Nanjing, China ; Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing, China ; Jiangsu Province's Key Medical Center for Digestive Disease Nanjing, China ; Institute of Hepatobiliary Surgery, Nanjing University Nanjing, China.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016026:Bone Marrow Transplantation; D024243:HMGB1 Protein / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D017114:Liver Failure, Acute / Q000378:metabolism* / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C000593874:Ager protein, rat; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D000067759:Receptor for Advanced Glycation End Products
keywords: Acute liver failure; Immuno-inflammatory reaction; bioartificial livers; high mobility group box chromosomal protein 1; soluble receptor for advanced glycation end products