Lipopolysaccharides protect mesenchymal stem cell against cardiac ischemia-reperfusion injury by HMGB1/STAT3 signaling  

作　　者：Jing-Yi WEN Hui-Xi PENG Dan WANG Zhi-Min WEN Yu-Tong LIU Jian QU Hong-Xuan CUI Yu-Ying WANG Yan-Lin DU Ting WANG Cong GENG Bing XU 

机构地区：[1]Department of Clinical Pharmacy,the Second Affiliated Hospital of Dalian Medical University,Dalian,Liaoning,China [2]Department of Pharmacy,the Second Affiliated Hospital of Inner Mongolia Medical University,Hohhot,Inner Mongolia,China [3]Department of Pharmacy,Ordos Central Hospital,Ordos,Inner Mongolia,China [4]Department of Clinical Laboratory,the Second Affiliated Hospital of Dalian Medical University,Dalian,Liaoning,China

出　　处：《Journal of Geriatric Cardiology》2023年第11期801-812,共12页老年心脏病学杂志（英文版）

基　　金：supported by grants from the Natural Science Foundation of Liaoning Province(No.2023-MS-268);Educational Committee Foundation of Liaoning Province(LJKZ0868);Funds for young and middle-aged disciplinary backbones of the Second Hospital of Dalian Medical University(No.dy2yxkgg 202002);partially supported by United Fund of the Second Hospital of Dalian Medical University and Dalian Institute of Chemical physics Chinese Academy of Sciences(No.UF-QN-202005).

摘　　要：BACKGROUND Myocardial ischemia-reperfusion(I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells(MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box1(HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3(STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown.METHODS In vitro, hypoxia/reoxygenation injury model was established by Anaero Pack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1and STAT3 by Western blot.RESULTS The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor(VEGF), hepatocyte growth factor(HGF), insulin growth factor(IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC.CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3signaling.

关 键 词：STAT3 HMGB1 ISCHEMIA 

分 类 号：R54[医药卫生—心血管疾病]