title: Hepatocyte growth factor enhances the barrier function in primary cultures of rat brain microvascular endothelial cells.
abstract: The effects of hepatocyte growth factor (HGF) on barrier functions were investigated by a blood-brain barrier (BBB) in vitro model comprising a primary culture of rat brain capillary endothelial cells (RBEC). In order to examine the response of the peripheral endothelial cells to HGF, human umbilical vascular endothelial cells (HUVEC) and human dermal microvascular endothelial cells (HMVEC) were also treated with HGF. HGF decreased the permeability of RBEC to sodium fluorescein and Evans blue albumin, and dose-dependently increased transendothelial electrical resistance (TEER) in RBEC. HGF altered the immunochemical staining pattern of F-actin bands and made ZO-1 staining more distinct on the linear cell borders in RBEC. In contrast, HGF increased sodium fluorescein and Evans blue albumin permeability in HMVEC and HUVEC, and decreased TEER in HMVEC. In HMVEC, HGF reduced cortical actin bands and increased stress fiber density, and increased the zipper-like appearance of ZO-1 staining. Western blot analysis showed that HGF significantly increased the amount of ZO-1 and VE-cadherin. HGF seems to act on the BBB to strengthen BBB integrity. These findings indicated that cytoskeletal rearrangement and cell-cell adhesion, such as through VE-cadherin and ZO-1, are candidate mechanisms for the influence of HGF on the BBB. The possibility that HGF has therapeutic significance in protecting the BBB from damage needs to be considered.
authors.affiliation: Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Omura 856-8562, Japan; Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 2-1001-1 Kubara, Omura 856-8562, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; BBB Laboratory, PharmaCo-Cell Company, Ltd., 1-43 Dejima, Nagasaki 850-0862, Japan. Electronic address: shin3@nagasaki-u.ac.jp.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Horai
authors.affiliation: Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Deli
authors.affiliation: Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Omura 856-8562, Japan; Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 2-1001-1 Kubara, Omura 856-8562, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.affiliation: Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; BBB Laboratory, PharmaCo-Cell Company, Ltd., 1-43 Dejima, Nagasaki 850-0862, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Niwa
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000098:blood supply*; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D055806:Microvessels / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D061251:Primary Cell Culture; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D062725:Tight Junction Proteins / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D062725:Tight Junction Proteins; D062826:Zonula Occludens-1 Protein; D000099152:Cadherin 5; C569044:Tjp1 protein, rat