Xinli Huang1, Yun Gao1, Jianjie Qin1, Sen Lu2. 1. Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, The Key Laboratory of Living Donor Liver Transplantation, National Health and Family Planning Commission, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. 2. Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, The Key Laboratory of Living Donor Liver Transplantation, National Health and Family Planning Commission, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. yin63992@163.com.
Abstract
OBJECTIVE: This study investigated the role of miR-214 in the hepatocyte apoptosis induced by hypoxia/reoxygenation (H/R) injury. MATERIALS AND METHODS: In vivo hepatic ischemia/reperfusion (HIR) injury, mice model and in vitro HR model were established. miR-214, TRAF1, ASK1, and JNK expression levels were detected by qRT-PCR and western blot. The apoptosis of mouse hepatocyte AML12 was detected by flow cytometry analysis. The interaction between miR-214 and TRAF1 was confirmed by dual-luciferase reporter gene assay. RESULTS: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated in HIR injury mice compared with sham mice. miR-214 expression was down-regulated in liver tissues of HIR and H/R-induced hepatocytes, whereas TRAF1, ASK1, and JNK expressions were up-regulated in HIR and H/R groups. H/R stimulation promoted the apoptosis of hepatocytes, and miR-214 overexpression inhibited the apoptosis of hepatocytes. Besides, TRAF1 was a target of miR-214 and negatively regulated by miR-214. miR-214/TRAF1 pathway involved in the modulation of H/R-induced apoptosis of hepatocytes. In vivo study proved miR-214 reduced hepatic injury of HIR mice. CONCLUSION: miR-214 overexpression reduces hepatocyte apoptosis after HIR injury through negatively regulating TRAF1/ASK1/JNK pathway.
OBJECTIVE: This study investigated the role of miR-214 in the hepatocyte apoptosis induced by hypoxia/reoxygenation (H/R) injury. MATERIALS AND METHODS: In vivo hepatic ischemia/reperfusion (HIR) injury, mice model and in vitro HR model were established. miR-214, TRAF1, ASK1, and JNK expression levels were detected by qRT-PCR and western blot. The apoptosis of mouse hepatocyte AML12 was detected by flow cytometry analysis. The interaction between miR-214 and TRAF1 was confirmed by dual-luciferase reporter gene assay. RESULTS: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated in HIR injury mice compared with sham mice. miR-214 expression was down-regulated in liver tissues of HIR and H/R-induced hepatocytes, whereas TRAF1, ASK1, and JNK expressions were up-regulated in HIR and H/R groups. H/R stimulation promoted the apoptosis of hepatocytes, and miR-214 overexpression inhibited the apoptosis of hepatocytes. Besides, TRAF1 was a target of miR-214 and negatively regulated by miR-214. miR-214/TRAF1 pathway involved in the modulation of H/R-induced apoptosis of hepatocytes. In vivo study proved miR-214 reduced hepatic injury of HIR mice. CONCLUSION:miR-214 overexpression reduces hepatocyte apoptosis after HIR injury through negatively regulating TRAF1/ASK1/JNK pathway.
Authors: Partha Mukhopadhyay; Mohanraj Rajesh; Béla Horváth; Sándor Bátkai; Ogyi Park; Galin Tanchian; Rachel Y Gao; Vivek Patel; David A Wink; Lucas Liaudet; György Haskó; Raphael Mechoulam; Pál Pacher Journal: Free Radic Biol Med Date: 2011-03-11 Impact factor: 7.376
Authors: Ali A Abdul-Sater; Maria I Edilova; Derek L Clouthier; Achire Mbanwi; Elisabeth Kremmer; Tania H Watts Journal: Nat Immunol Date: 2016-11-28 Impact factor: 25.606
Authors: X-F Zhang; R Zhang; L Huang; P-X Wang; Y Zhang; D-S Jiang; L-H Zhu; S Tian; X-D Zhang; H Li Journal: Cell Death Dis Date: 2014-10-16 Impact factor: 8.469