title: Liver-specific Prox1 inactivation causes hepatic injury and glucose intolerance in mice.
abstract: Previous reports have revealed that Prospero-related homeobox 1 (Prox1) is required for the migration and differentiation of hepatoblasts during embryonic liver formation. However, the role of Prox1 in adults remains to be elucidated. We created liver-specific Prox1 knockout mice to verify the role of Prox1 in adult hepatocytes. The mutant mice exhibit hepatic injury and a nonobese, insulin-resistant diabetic phenotype in vivo. Hepatocyte injury is observed predominantly in the perivenous region and is characterized by the formation of vacuoles and emergence of round-shaped mitochondria, suggesting that the effect of Prox1 on the maintenance of adult hepatocytes is region dependent. Furthermore, glycolysis is suppressed, and both oxidative phosphorylation and autophagy are upregulated in the livers of Prox1 knockout mice, indicating that Prox1 has a role in regulating energy homeostasis in hepatocytes.
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Internal Medicine, Al-Azhar University, Cairo, Egypt.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Elbahrawy
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Furuyama
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Horiguchi
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hosokawa
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tsuboi
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Morito
authors.initials: M
authors.lastname: Sakikubo
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.|Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Masui
authors.affiliation: Department of Gastrointestinal Surgery, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kubo
authors.affiliation: Department of Gastrointestinal Surgery, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Department of Clinical Application, Center for iPS cell Research and Application, Kyoto, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawaguchi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000235:genetics; D015870:Gene Expression; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008930:Mitochondria, Liver / Q000378:metabolism / Q000648:ultrastructure; D009928:Organ Specificity; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein
keywords: Prospero-related homeobox 1; glycolysis; type 2 diabetes