title: Inositol-requiring enzyme 1-mediated endoplasmic reticulum stress triggers apoptosis and fibrosis formation in liver cirrhosis rat models.
abstract: Long‑term and advanced cirrhosis is usually irreversible and often coincides with variceal hemorrhage or development of hepatocellular carcinoma; therefore, liver cirrhosis is a major cause of morbidity and mortality globally. The aim of the present study was to investigate the specific mechanism behind the formation of fibrosis or cirrhosis using rat models of hepatic fibrosis. The cirrhosis model was established by intraperitoneally administering dimethylnitrosamine to the rats. Hematoxylin and eosin staining was performed on the hepatic tissues of the rats to observe the fibrosis or cirrhosis, and western blot analysis was employed to detect α‑smooth muscle actin and desmin protein expression. Flow cytometric analysis was used to examine early and late apoptosis, and the protein and mRNA expression of endoplasmic reticulum (ER) stress-associated unfolded protein response (UPR) pathway proteins and apoptotic proteins [C/EBP homologous protein (CHOP) and caspase‑12] was detected by western blotting and the reverse-transcription polymerase chain reaction, respectively. The results indicated that the cirrhosis model was established successfully and that fibrosis was significantly increased in the cirrhosis model group compared with that in the normal control group. Flow cytometric analysis showed that early and late apoptosis in the cirrhosis model was significantly higher compared with that in the control group. The expression of the UPR pathway protein inositol-requiring enzyme (IRE) 1, as well as the expression of CHOP, was increased significantly in the cirrhotic rat tissues compared with that in the control group tissues (P<0.05). In conclusion, apoptosis was clearly observed in the hepatic tissue of cirrhotic rats, and the apoptosis was caused by activation of the ER stress-mediated IRE1 and CHOP.
authors.affiliation: Department of Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Tianpeng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Lizhou
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Radiology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Shi
authors.initials: S
authors.lastname: Zhou
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000378:metabolism; D056811:Unfolded Protein Response; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D004722:Endoribonucleases; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D051742:Transcription Factor CHOP; D019892:eIF-2 Kinase; C575026:Ern1 protein, rat