title: Hepatocyte Is a Sole Cell Type Responsible for the Production of Coagulation Factor IX In Vivo.
abstract: Coagulation factor IX (FIX) is synthesized by hepatocytes, and the lack of this protein causes hemophilia B. Liver nonparenchymal cells, including liver sinusoidal endothelial cells (LSECs) and extrahepatic cells in the body, are scarcely shown to have an ability to synthesize and secrete FIX. The present study investigated the existence of cells responsible for synthesizing FIX other than hepatocytes in mice using gene expression analyses and FIX-specific clotting assays. Among the several organs investigated, including liver, lung, spleen, kidney, brain, intestine, and tongue, FIX mRNA expressions were observed only in the liver. From the liver, hepatocytes and LSECs were isolated. FIX mRNA expression and FIX protein secretion were observed exclusively in the hepatocytes. Furthermore, the clotting activity of FIX secreted from the cultured hepatocytes was found to be dependent on the concentration of vitamin K2. These findings indicated that the hepatocyte is the only cell type that biochemically produces functional FIX in vivo. This highlights the importance of hepatocytes or cells that are fully differentiated toward the hepatic lineage for possible application for regenerative medicine and for targeting gene delivery to establish new cell-based treatments for hemophilia B.
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University , Shinjuku, Tokyo , Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University , Shinjuku, Tokyo , Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University , Shinjuku, Tokyo , Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Mukobata
authors.affiliation: † First Department Medicine, Nara Medical University , Kashihara, Nara , Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kubo
authors.affiliation: ‡ Department of Surgery, Nara Medical University , Kashihara, Nara , Japan.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Koyama
authors.affiliation: ‡ Department of Surgery, Nara Medical University , Kashihara, Nara , Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
authors.affiliation: § Department of Pediatrics, Nara Medical University , Kashihara, Nara , Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University , Shinjuku, Tokyo , Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
keywords: Factor IX; Hemophilia B; Hepatocyte; Nonparenchymal cell