title: Deceleration of liver regeneration by knockdown of augmenter of liver regeneration gene is associated with impairment of mitochondrial DNA synthesis in mice.
abstract: Hepatic stimulator substance, also known as augmenter of liver regeneration (ALR), is a novel hepatic mitogen that stimulates liver regeneration after partial hepatectomy (PH). Recent work has indicated that a lack of ALR expression inhibited liver regeneration in rats, and the mechanism seems to be related to increased cell apoptosis. The mitochondria play an important role during liver regeneration. Adequate ATP supply, which is largely dependent on effective mitochondrial biogenesis, is essential for progress of liver regeneration. However, ALR gene expression during liver regeneration, particularly its function with mitochondrial DNA synthesis, remains poorly understood. In this study, ALR expression in hepatocytes of mice was suppressed with ALR short-hairpin RNA interference or ALR deletion (knockout, KO). The ALR-defective mice underwent PH, and the liver was allowed to regenerate for 1 wk. Analysis of liver growth and its correlation with mitochondrial biogenesis showed that both ALR mRNA and protein levels increased robustly in control mice with a maximum at days 3 and 4 post-PH. However, ALR knockdown inhibited hepatic DNA synthesis and decelerated liver regeneration after PH. Furthermore, both in the ALR-knockdown and ALR-KO mice, expression of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-γ coactivator-1α were reduced, resulting in impaired mitochondrial biogenesis. In conclusion, ALR is apparently required to ensure appropriate liver regeneration following PH in mice, and deletion of the ALR gene may delay liver regeneration in part due to impaired mitochondrial biogenesis.
authors.affiliation: Department of Cell Biology and Municipal Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China; and.
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Han
authors.affiliation: Department of Cell Biology and Municipal Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China; and.
authors.forename: Ling-yue
authors.initials: LY
authors.lastname: Dong
authors.affiliation: Department of Cell Biology and Municipal Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China; and.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Cell Biology and Municipal Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China; and.
authors.forename: Guang-yong
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Cell Biology and Municipal Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China; and anwei@ccmu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cell Biology and Municipal Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China; and.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Surgery, University of Munich, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thasler
authors.affiliation: Department of Cell Biology and Municipal Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China; and.
authors.forename: Wei
authors.initials: W
authors.lastname: An
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D049109:Cell Proliferation; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008115:Liver Regeneration; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000473:pathology; D063269:Mitochondrial Turnover; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; D050862:Oxidoreductases Acting on Sulfur Group Donors; C551231:GFER protein, mouse
keywords: augmenter of liver regeneration; hepatic stimulator substance; liver regeneration; mitochondrial biogenesis