title: Gene expression profiling reveals the mechanism and pathophysiology of mouse liver regeneration.
abstract: Comprehensive analysis of the changes in gene expression during liver regeneration was carried out by using an in-house microarray composed of 2,304 distinct mouse liver cDNA clones. Mice were subjected to partial two-thirds hepatectomy, and changes in mRNA levels were monitored up to 48 h. Of the 2,304 genes analyzed, 496 genes showed expression levels measurable at all time points after the partial hepatectomy. 317 genes were up- or down-regulated 2-fold or more at least at one time point during liver regeneration and were classified into eight clusters based on their expression patterns. With a more stringent cut-off value of +/-2 S.D., 68 genes were listed and were classified into five clusters. In these two analyses with different clustering criteria, functionally categorized genes showed similar cluster distributions. Genes involved in protein synthesis and posttranslational processing were significantly enriched in the cluster characterized by rapid gene activation and subsequent persistence. This suggests the importance of modulating the efficiency of protein supply and/or altering the composition of protein population from the early phase of hepatocyte proliferation. Genes for two major liver functions, i.e. plasma protein secretion and intermediate metabolism were enriched in distinct clusters exhibiting the features of gradual gene activation and sustained repression, respectively. Therefore, these genes are differentially regulated during the regeneration, possibly leading to changes in the flow of amino acids and energy from enzyme proteins to plasma proteins in their synthesis. Thus, clustering analysis of expression patterns of functionally classified genes gave insights into mechanism and pathophysiology of liver regeneration.
authors.affiliation: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Chiba
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Junya
authors.initials: J
authors.lastname: Hashida
authors.forename: Youji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Saisho
authors.forename: Masaki
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology; D008099:Liver / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration; D013997:Time Factors; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger