title: [Blocking extracellular HMGB1 activity protects against doxorubicin induced cardiac injury in mice].
abstract: This study aims to investigate the preventive role and potential mechanisms of blocking extracellular HMGB1 function on doxorubicin induced cardiac injury. Mice were treated with HMGB1 blocker glycyrrhizin 1 h before and one time every day (intraperitoneal, 10 mg per mouse) after doxorubicin injection, and sacrificed on the day 14 after doxorubicin challenge. Cardiac function was evaluated by echocardiography and hemodynamic measurement. Myocardial inflammation and collagen deposition were analyzed by immunohistochemistry and picrosirius red staining. The interaction of HMGB1 and TLR2 was assessed by co-immunoprecipitation and confocal microscopy. The protein contents of HMGB1, MyD88, p65NF-kappaB and phospho-p65NF-kappaB were measured by Immunoblot. Compared with mice treated with saline, doxorubicin treatment led to an upregulation in HMGB1 expression. Blocking HMGB1 activity with glycyrrhizin protected mice against cardiac dysfunction, inflammatory response, and cardiac fibrosis induced by doxorubicin challenge. Glycyrrhizin inhibited the interaction of HMGB1 and TLR2, and blocked the downstream signaling of TLR2. In conclusion, blocking HMGB1 protected against doxorubicin induced cardiac injury by inhibiting TLR2 signaling pathway.
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors: Yong-Gang
authors: YG
authors: Ma
authors: Xiao-Wei
authors: XW
authors: Zhang
authors: Hua-Yan
authors: HY
authors: Bao
authors: Shi-Shan
authors: SS
authors: Yu
authors: Zhuo-Wei
authors: ZW
authors: Hu
authors: Wei
authors: W
authors: Sun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D004317:Doxorubicin; D004347:Drug Interactions; D005355:Fibrosis; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D047468:Immunoprecipitation; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D024243:HMGB1 Protein; D020381:Interleukin-17; D051195:Toll-Like Receptor 2; D053773:Transforming Growth Factor beta1; D019695:Glycyrrhizic Acid; D004317:Doxorubicin; D003094:Collagen