PMID- 24370951 OWN - NLM STAT- MEDLINE DCOM- 20150219 LR - 20140317 IS - 1095-9319 (Electronic) IS - 0026-2862 (Linking) VI - 92 DP - 2014 Mar TI - Hepatocyte growth factor enhances the barrier function in primary cultures of rat brain microvascular endothelial cells. PG - 41-9 LID - S0026-2862(13)00205-7 [pii] LID - 10.1016/j.mvr.2013.12.004 [doi] AB - 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. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Yamada, Narumi AU - Yamada N AD - 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. FAU - Nakagawa, Shinsuke AU - Nakagawa S AD - 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. FAU - Horai, Shoji AU - Horai S AD - Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. FAU - Tanaka, Kunihiko AU - Tanaka K AD - Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. FAU - Deli, Maria A AU - Deli MA AD - Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary. FAU - Yatsuhashi, Hiroshi AU - Yatsuhashi H AD - 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. FAU - Niwa, Masami AU - Niwa M AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131223 PL - United States TA - Microvasc Res JT - Microvascular research JID - 0165035 RN - 0 (Actins) RN - 0 (Antigens, CD) RN - 0 (Cadherins) RN - 0 (Tight Junction Proteins) RN - 0 (Tjp1 protein, rat) RN - 0 (Zonula Occludens-1 Protein) RN - 0 (cadherin 5) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Actins/metabolism MH - Animals MH - Antigens, CD/metabolism MH - Blood-Brain Barrier/*cytology/drug effects/*physiology MH - Brain/*blood supply MH - Cadherins/metabolism MH - Capillary Permeability/drug effects/physiology MH - Cell Adhesion/physiology MH - Cells, Cultured MH - Endothelial Cells/drug effects/*physiology MH - Hepatocyte Growth Factor/pharmacology/*physiology MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Microvessels/cytology/drug effects/physiology MH - Primary Cell Culture MH - Proto-Oncogene Proteins c-met/metabolism MH - Rats MH - Tight Junction Proteins/metabolism MH - Zonula Occludens-1 Protein/metabolism EDAT- 2013/12/29 06:00 MHDA- 2015/02/20 06:00 CRDT- 2013/12/28 06:00 PHST- 2013/09/25 00:00 [received] PHST- 2013/12/04 00:00 [revised] PHST- 2013/12/16 00:00 [accepted] PHST- 2013/12/28 06:00 [entrez] PHST- 2013/12/29 06:00 [pubmed] PHST- 2015/02/20 06:00 [medline] AID - S0026-2862(13)00205-7 [pii] AID - 10.1016/j.mvr.2013.12.004 [doi] PST - ppublish SO - Microvasc Res. 2014 Mar;92:41-9. doi: 10.1016/j.mvr.2013.12.004. Epub 2013 Dec 23.