title: Inhibition of the proliferation and acceleration of migration of vascular endothelial cells by increased cysteine-rich motor neuron 1.
abstract: Cysteine-rich motor neuron 1 (CRIM1) is upregulated only in extracellular matrix gels by angiogenic factors such as vascular endothelial growth factor (VEGF). It then plays a critical role in the tube formation of endothelial cells. In the present study, we investigated the effects of increased CRIM1 on other endothelial functions such as proliferation and migration. Knock down of CRIM1 had no effect on VEGF-induced proliferation or migration of human umbilical vein endothelial cells (HUVECs), indicating that basal CRIM1 is not involved in the proliferation or migration of endothelial cells. Stable CRIM1-overexpressing endothelial F-2 cells, termed CR1 and CR2, were constructed, because it was difficult to prepare monolayer HUVECs that expressed high levels of CRIM1. Proliferation was reduced and migration was accelerated in both CR1 and CR2 cells, compared with normal F-2 cells. Furthermore, the transient overexpression of CRIM1 resulted in decreased proliferation and increased migration of bovine aortic endothelial cells. In contrast, neither proliferation nor migration of COS-7 cells were changed by the overexpression of CRIM1. These results demonstrate that increased CRIM1 reduces the proliferation and accelerates the migration of endothelial cells. These CRIM1 effects might contribute to tube formation of endothelial cells. CRIM1 induced by angiogenic factors may serve as a regulator in endothelial cells to switch from proliferating cells to morphological differentiation.
authors.affiliation: Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan.
authors.forename: Mayuka
authors.initials: M
authors.lastname: Morimoto
authors.affiliation: Department of Dermatology, Kitano Hospital, The Tazuke Kofukai Nedical Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Toda
authors.affiliation: Department of Clinical Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Shinya
authors.affiliation: Department of Clinical Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan; Institute for Biosciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan. Electronic address: imwalrus@mukogawa-u.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D052004:Bone Morphogenetic Protein Receptors; D019556:COS Cells; D002417:Cattle; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002522:Chlorocebus aethiops; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: C486175:CRIM1 protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D052004:Bone Morphogenetic Protein Receptors
keywords: Angiogenesis; CRIM1; Endothelial; Migration; Proliferation