title: Overexpression of the long noncoding RNA TUG1 protects against cold-induced injury of mouse livers by inhibiting apoptosis and inflammation.
abstract: Hepatic injury provoked by cold storage is a major problem affecting liver transplantation, as exposure to cold induces apoptosis in hepatic tissues. Long noncoding RNAs (lncRNAs) are increasingly understood to regulate apoptosis, but the contribution of lncRNAs to cold-induced liver injury remains unknown. Using RNA-seq, we determined the differential lncRNA expression profile in mouse livers after cold storage and found that expression of the lncRNA TUG1 was significantly down-regulated. Overexpression of TUG1 attenuated cold-induced apoptosis in mouse hepatocytes and liver sinusoidal endothelial cells LSECs, in part by blocking mitochondrial apoptosis and endoplasmic reticulum (ER) stress pathways. Moreover, TUG1 attenuated apoptosis, inflammation, and oxidative stress in vivo in livers subjected to cold storage. Overexpression of TUG1 also improved hepatocyte function and prolonged hepatic graft survival rates in mice. These results suggest that the lncRNA TUG1 exerts a protective effect against cold-induced liver damage by inhibiting apoptosis in mice, and suggests a potential role for TUG1 as a target for the prevention of cold-induced liver damage in liver transplantation.
  
  
  METHODS
  RNA-seq data are available from GEO using accession number GSE76609.
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Luzhou Medical College, Sichuan Province, China.
authors.forename: Song
authors.initials: S
authors.lastname: Su
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Luzhou Medical College, Sichuan Province, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Luzhou Medical College, Sichuan Province, China.
authors.forename: Kai
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Luzhou Medical College, Sichuan Province, China.
authors.forename: Mengyu
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Luzhou Medical College, Sichuan Province, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Luzhou Medical College, Sichuan Province, China.
authors.forename: Fangyi
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Luzhou Medical College, Sichuan Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Luzhou Medical College, Sichuan Province, China.
authors.forename: Xianming
authors.initials: X
authors.lastname: Xia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015152:Blotting, Northern; D015153:Blotting, Western; D003080:Cold Temperature; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D006085:Graft Survival / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation / Q000379:methods; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D062085:RNA, Long Noncoding; C500572:TUG1 noncoding RNA, mouse
keywords: RNA-seq; apoptosis; cold injury; inflammation; liver; lncRNA TUG1; long noncoding RNA