PMID- 29842876
OWN - NLM
STAT- MEDLINE
DCOM- 20190924
LR  - 20190925
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 369
IP  - 2
DP  - 2018 Aug 15
TI  - Vascular endothelial growth factor aggravates cerebral ischemia and 
      reperfusion-induced blood-brain-barrier disruption through regulating 
      LOC102640519/HOXC13/ZO-1 signaling.
PG  - 275-283
LID - S0014-4827(18)30300-8 [pii]
LID - 10.1016/j.yexcr.2018.05.029 [doi]
AB  - BACKGROUND/OBJECTIVE: Vascular endothelial growth factor (VEGF) has been 
      recognized to be a potential pharmaceutical target for treating ischemic stroke, 
      but its severe side effects hinder its widely application. Here, the present 
      study was designed to investigate the effects of VEGF on blood-brain-barrier 
      (BBB) disruption and the underlying mechanisms. METHODS: A mouse model of middle 
      cerebral artery occlusion (MCAO) was constructed and treated with or without 
      VEGF. Meanwhile, mice brain microvascular endothelial cells in co-culture with 
      astrocytes were subjected to 1, 2 and 4 h oxygen-glucose deprivation followed by 
      24 h of reperfusion (OGD/R) in the absence or presence of VEGF. The mRNA and 
      protein expression were assessed by real-time PCR and Western blotting. 
      Fluorescence in situ hybridization (FISH) was utilized to validate LOC102640519 
      expression in OGD/R cell models. Chromatin Immunoprecipitation (ChIP) assay was 
      used to confirm the regulatory mechanism of LOC102640519 to HOXC13. Interactions 
      between HOXC13 and ZO-1 were measured by a luciferase reporter assay and RNA pull 
      down assay. RESULTS: Our results showed that administration of VEGF significantly 
      aggravated BBB by upregulating LOC102640519 and HOXC13 expression in vitro and 
      vitro model of cerebral ischemia. Furthermore, LOC102640519 positively regulated 
      the expression of HOXC13, thus negatively regulated the expression of ZO-1, 
      Occludin and Claudin-5 in OGD/R model in the absence or presence of VEGF. 
      CONCLUSIONS: VEGF aggravated BBB disruption after cerebral I/R-induced injury 
      probably by increasing LOC102640519 and HOXC13 through inhibition of ZO-1, 
      Occludin and Claudin-5.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Wu, Li
AU  - Wu L
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Ye, Zeming
AU  - Ye Z
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Pan, Ying
AU  - Pan Y
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Li, Xianliang
AU  - Li X
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Fu, Xian
AU  - Fu X
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Zhang, Bo
AU  - Zhang B
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Li, Youfu
AU  - Li Y
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Lin, Wanrong
AU  - Lin W
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Li, Xuelong
AU  - Li X
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Gao, Qingchun
AU  - Gao Q
AD  - Institute of Neuroscience and Department of Neurology, the Second Affiliated 
      Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: 
      gaoqc163@yeah.net.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180526
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hoxc13 protein, mouse)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Tight Junction Proteins)
RN  - 0 (Tjp1 protein, mouse)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - 0 (vascular endothelial growth factor A, mouse)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/drug effects/*metabolism
MH  - Brain Ischemia/*etiology/genetics/*metabolism
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Gene Knockdown Techniques
MH  - Homeodomain Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RNA, Long Noncoding/genetics/*metabolism
MH  - Reperfusion Injury/*etiology/genetics/*metabolism
MH  - Signal Transduction
MH  - Tight Junction Proteins/genetics/metabolism
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A/*administration & dosage/*metabolism
MH  - Zonula Occludens-1 Protein/genetics/*metabolism
OTO - NOTNLM
OT  - Blood-brain-barrier
OT  - HOXC13
OT  - Ischemic stroke
OT  - LOC102640519
OT  - Vascular endothelial growth factor
OT  - ZO-1
EDAT- 2018/05/31 06:00
MHDA- 2019/09/26 06:00
CRDT- 2018/05/30 06:00
PHST- 2018/01/25 00:00 [received]
PHST- 2018/05/23 00:00 [revised]
PHST- 2018/05/24 00:00 [accepted]
PHST- 2018/05/31 06:00 [pubmed]
PHST- 2019/09/26 06:00 [medline]
PHST- 2018/05/30 06:00 [entrez]
AID - S0014-4827(18)30300-8 [pii]
AID - 10.1016/j.yexcr.2018.05.029 [doi]
PST - ppublish
SO  - Exp Cell Res. 2018 Aug 15;369(2):275-283. doi: 10.1016/j.yexcr.2018.05.029. Epub 
      2018 May 26.