title: Coagulation factor IX regulates cell migration and adhesion in vitro.
abstract: Coagulation factor IX is thought to circulate in the blood as an inactive zymogen before being activated in the coagulation process. The effect of coagulation factor IX on cells is poorly understood. This study aimed to evaluate the effects of intact coagulation factor IX and its cleavage fragments on cell behavior. A431 cells (derived from human squamous cell carcinoma), Pro5 cells (derived from mouse embryonic endothelial cells), Cos7 cells, and human umbilical vein endothelial cells were utilized in this study. The effects of coagulation factor IX and its cleavage fragments on cell behavior were investigated in several types of experiments, including wound-healing assays and modified Boyden chamber assays. The effect of coagulation factor IX depended on its processing; full-length coagulation factor IX suppressed cell migration, increased adhesion to matrix, and enhanced intercellular adhesion. In contrast, activated coagulation factor IX enhanced cell migration, suppressed adhesion to matrix, and inhibited intercellular adhesion. An activation peptide that is removed during the coagulation process was found to be responsible for the activity of full-length coagulation factor IX, and the activity of activated coagulation factor IX was localized to an EGF domain of the coagulation factor IX light chain. Full-length coagulation factor IX has a sedative effect on cells, which is counteracted by activated coagulation factor IX in vitro. Thus, coagulation factor IX may play roles before, during, and after the coagulation process.
authors.affiliation: Division of Dental Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kitano
authors.affiliation: Division of Dental Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mamiya
authors.affiliation: Division of Physiology, Department of Biomedical Science, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Ishikawa
authors.initials: I
authors.lastname: Tomomi
authors.affiliation: Division of Physiology, Department of Biomedical Science, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Kokubun
authors.initials: K
authors.lastname: Shinichiro
authors.affiliation: Division of Physiology, Department of Biomedical Science, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Hidai
authors.initials: H
authors.lastname: Chiaki
mesh_terms: D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D005164:Factor IX / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice
chemical_list: D005164:Factor IX
keywords: EGF motif; activation peptide; adhesion; coagulation factor; de-adhesion; migration