title: Cellular density regulation of plasminogen gene expression in mouse hepatocytes.
abstract: The liver produces a variety of proteins including plasminogen. Plasminogen is pro-enzyme that is converted into plasmin by plasminogen activator. Plasmin has a broad substrate spectrum and participates in several biological processes, such as fibrinolysis, tissue remodeling, cell migration, angiogenesis and embryogenesis. In the present study, the regulation of plasminogen expression in mouse hepatocytes was investigated in the primary culture system. Expression level of plasminogen mRNA in the culture at the low cell density condition (0.2 x 10(5) cells / cm(2)) was compared with that at the high cell density condition (1.0 x 10 (5) cells / cm(2)). In the low cell density culture, the expression level of plasminogen mRNA decreased by a time-dependent manner. However, mRNAs for albumin and alpha(2)-antiplasmin were not influenced by the low cell density culture. On the other hand, in the high cell density culture, plasminongen mRNA expressed constantly as well as albumin and alpha(2)-antiplasmin mRNAs. Thus, the decrease in plasminogen mRNA expression could specifically occur when the density of hepatocytes was low. The down-regulation of plasminogen mRNA in the low cell density culture is not observed in the presence of cycloheximide, suggesting that the de novo protein synthesis is required for the regulatory mechanism. These findings indicate that the expression of plasminogen mRNA from hepatocyte is dependent on the cell density and the stimulation by cell-cell contact may be an important factor for the constitutive expression of plasminogen gene in hepatocytes.
authors.affiliation: Department of Physiology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama-city, 589-8511 Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Akao
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ueshima
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okada
authors.forename: Hideharu
authors.initials: H
authors.lastname: Fukao
authors.forename: Taiichiro
authors.initials: T
authors.lastname: Seki
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Ariga
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
mesh_terms: D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D015342:DNA Probes; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism* / Q000502:physiology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010958:Plasminogen / Q000096:biosynthesis* / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D000979:alpha-2-Antiplasmin / Q000096:biosynthesis
chemical_list: D000418:Albumins; D015342:DNA Probes; D018076:DNA, Complementary; D006133:Growth Substances; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D000979:alpha-2-Antiplasmin; D010958:Plasminogen