title: Endothelial connexin32 enhances angiogenesis by positively regulating tube formation and cell migration.
abstract: The gap junction proteins connexin32 (Cx32), Cx37, Cx40, and Cx43 are expressed in endothelial cells, and regulate vascular functions involving inflammation, vasculogenesis and vascular remodeling. Aberrant Cxs expression promotes the development of atherosclerosis which is modulated by angiogenesis; however the role played by endothelial Cxs in angiogenesis remains unclear. In this study, we determined the effects of endothelial Cxs, particularly Cx32, on angiogenesis. EA.hy926 cells that had been transfected to overexpress Cx32 significantly increased capillary length and the number on branches compared to Cx-transfectant cells over-expressing Cx37, Cx40, and Cx43 or mock-treated cells. Treatment via intracellular transfer of anti-Cx32 antibody suppressed tube formation of human umbilical vein endothelial cells (HUVECs) compared to controls. In vitro wound healing assays revealed that Cx32-transfectant cells significantly increased the repaired area while anti-Cx32 antibody-treated HUVECs reduced it. Ex vivo aorta ring assays and in vivo matrigel plaque assays showed that Cx32-deficient mice impaired both vascular sprouting from the aorta and cell migration into the implanted matrigel. Therefore endothelial Cx32 facilitates tube formation, wound healing, vascular sprouting, and cell migration. Our results suggest that endothelial Cx32 positively regulates angiogenesis by enhancing endothelial cell tube formation and cell migration.
authors: Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu-city, Mie 514-8507, Japan.
authors: Takayuki
authors: T
authors: Okamoto
authors: Faculty of Medical Engineering, Suzuka University of Medical Science, 1001-1 Kishioka-cho, Suzuka-city, Mie 510-0293, Japan.
authors: Nobuyuki
authors: N
authors: Akita
authors: Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu-city, Mie 514-8507, Japan; Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507, Japan.
authors: Eiji
authors: E
authors: Kawamoto
authors: Department of Biochemistry, Mie Prefecture College of Nursing, 1-1-1 Yumegaoka, Tsu-city, Mie 514-0116, Japan.
authors: Tatsuya
authors: T
authors: Hayashi
authors: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka City 513-8679, Japan.
authors: Koji
authors: K
authors: Suzuki
authors: Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu-city, Mie 514-8507, Japan. Electronic address: shimaoka@doc.medic.mie-u.ac.jp.
authors: Motomu
authors: M
authors: Shimaoka
mesh_terms: D000818:Animals; D002196:Capillaries / Q000254:growth & development / Q000502:physiology; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D017630:Connexins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics*; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D000097002:Gap Junction beta-1 Protein
keywords: Angiogenesis; Cell migration; Endothelial cells; Gap junctions; Tube formation