Effects of bone marrow MSCs transfected with sRAGE on the intervention of HMGB1 induced immuno-inflammatory reaction.

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. CONCLUSION: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.