Caspase-3/Treg and PI3K/AKT/mTOR pathway is involved in Liver Ischemia Reperfusion Injury (IRI) protection by everolimus |
| |
| Affiliation: | 1. Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul/UFRGS, Brazil;2. Hospital de Clínicas de Porto Alegre/HCPA, Brazil;3. Universidade Federal do Rio Grande do Sul/UFRGS, Brazil;1. Department of Gastroenterology, The 940th Hospital of Joint Service Logistics Support Force of Chinese People''s Liberation Army, Lanzhou 730050, Gansu, China;2. The First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, Gansu, China;1. Medical Research Center, Affiliated Hospital of Jining Medical University, Jining, PR China;2. Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, PR China;3. Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, PR China;4. Jilin University No 3 Hospital, Jilin, PR China;5. Shanghai Meifeng Biotechnology Co., Ltd, Shanghai, PR China;6. Institute of Liver Diseases, Affiliated Hospital of Jining Medical University, Jining, PR China;1. ICU Fellow in National Hepatology and Tropical Medicine Research Institute (NHTNMRI), Cairo, Egypt;2. Ain Shams University, Egypt;3. National Cancer Institute, Cairo University, Egypt;1. Liver Transplant Institute, Inonu University Faculty of Medicine, 44280 Malatya, Turkey;2. Department of Medical Biochemistry, Inonu University Faculty of Medicine, 44280 Malatya, Turkey;3. Department of Surgery, Kenyatta University Teaching, Referral and Research Hospital, 00100 Nairobi, Kenya;4. Fuel-Oil Analysis Laboratory, Inonu University Rectorate, 44280 Malatya, Turkey |
| |
| Abstract: | Ischemia-reperfusion injury (IRI) of the liver is a severe complication that can follow hemorrhagic shock and liver surgery. Regulatory T cells (Treg) show the potential of improving outcomes of IRI. Everolimus is an mTOR inhibitor used in liver transplantation and the treatment of tumor patients through PI3K/AKT/mTOR pathway. The present study was designed to investigate the efficacy and mechanism of everolimus on Treg for the treatment of IRI. Hepatocytes were exposed to H2O2 and hypoxic conditions to investigate the effects of everolimus on reactive oxygen species ROS-induced and H/R-induced injury in vitro. The effects of everolimus on liver IRI were investigated in a warm ischemia liver model in vivo. Our results indicate that everolimus markedly protected liver IRI in vivo and vitro. Furthermore, everolimus increased the levels of phospho- (p-)AKT, p-mTOR but not p-GSK following IRI. Taken together, our data showed that everolimus protected against IRI via regulation of caspase-3/Treg and the PI3K/AKT/mTOR signalling pathway, which provides new insight into the treatment of liver IRI. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
