title: Localization of ADAMTS13 to the stellate cells of human liver.
abstract: Although the chromosomal localization (9q34) of the gene encoding the human form of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13) and its exclusive expression in the liver have been established, the cells that produce this enzyme are yet to be determined. We investigated the expression of ADAMTS13 mRNA and protein in fresh frozen specimens obtained during liver biopsies of 8 patients with liver diseases. In situ hybridizations to localize ADAMTS13 mRNA showed positive signals exclusively in perisinusoidal cells with irregularly elongated dendritic processes extending between hepatocytes. Furthermore, ADAMTS13 was detected immunohistochemically in perisinusoidal cells, whereas no staining was observed in hepatocytes. The positive cells varied in shape from unipolar to dendritic with irregularly elongated cytoplasmic processes, features common to hepatic stellate cells (HSCs). Double-labeling experiments revealed that the ADAMTS13-positive cells also expressed alpha-smooth muscle actin, confirming that these cells were activated HSCs. These results suggest that HSCs may be major cells producing ADAMTS13 in human liver.
authors.affiliation: Third Department of Internal Medicine, Department of Anatomy, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara, 634-8522, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Uemura
authors.forename: Kouko
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Masao
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Tomomi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Iwamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Mori
authors.forename: Akio
authors.initials: A
authors.lastname: Wanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D048430:Cell Shape; D022081:Cell Surface Extensions / Q000737:chemistry; D005260:Female; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology* / Q000201:enzymology*; D008297:Male; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D014018:Tissue Distribution
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human