PMID- 23428182
OWN - NLM
STAT- MEDLINE
DCOM- 20140116
LR  - 20181202
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 34
IP  - 7
DP  - 2013 Jul
TI  - Advanced glycation end-products disrupt the blood-brain barrier by stimulating 
      the release of transforming growth factor-beta by pericytes and vascular endothelial 
      growth factor and matrix metalloproteinase-2 by endothelial cells in vitro.
PG  - 1902-12
LID - S0197-4580(13)00042-0 [pii]
LID - 10.1016/j.neurobiolaging.2013.01.012 [doi]
AB  - Diabetic encephalopathy is now accepted as an important complication of diabetes. 
      The breakdown of the blood-brain barrier (BBB) is associated with dementia in 
      patients with type 2 diabetes mellitus (T2DM). The purpose of this study was to 
      identify the possible mechanisms responsible for the disruption of the BBB after 
      exposure to advanced glycation end-products (AGEs). We investigated the effect of 
      AGEs on the basement membrane and the barrier property of the BBB by Western blot 
      analysis, using our newly established lines of human brain microvascular 
      endothelial cell (BMEC), pericytes, and astrocytes. AGEs reduced the expression 
      of claudin-5 in BMECs by increasing the autocrine signaling through vascular 
      endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) secreted 
      by the BMECs themselves. Furthermore, AGEs increased the amount of fibronectin in 
      the pericytes through a similar up-regulation of the autocrine transforming 
      growth factor (TGF)-beta released by pericytes. These results indicated that AGEs 
      induce basement membrane hypertrophy of the BBB by increasing the degree of 
      autocrine TGF-beta signaling by pericytes, and thereby disrupt the BBB through the 
      up-regulation of VEGF and MMP-2 in BMECs under diabetic conditions.
CI  - Copyright (c) 2013. Published by Elsevier Inc.
FAU - Shimizu, Fumitaka
AU  - Shimizu F
AD  - Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate 
      School of Medicine, Ube, Japan.
FAU - Sano, Yasuteru
AU  - Sano Y
FAU - Tominaga, Osamu
AU  - Tominaga O
FAU - Maeda, Toshihiko
AU  - Maeda T
FAU - Abe, Masa-aki
AU  - Abe MA
FAU - Kanda, Takashi
AU  - Kanda T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130219
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 3.4.24.24 (MMP2 protein, human)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/drug effects/*metabolism
MH  - Cell Line, Transformed
MH  - Cells, Cultured
MH  - Endothelial Cells/drug effects/*metabolism
MH  - Glycation End Products, Advanced/*toxicity
MH  - Humans
MH  - Matrix Metalloproteinase 2/*biosynthesis
MH  - Pericytes/drug effects/*metabolism
MH  - Rats
MH  - Transforming Growth Factor beta/*biosynthesis/metabolism
MH  - Up-Regulation/*physiology
MH  - Vascular Endothelial Growth Factor A/*biosynthesis
EDAT- 2013/02/23 06:00
MHDA- 2014/01/17 06:00
CRDT- 2013/02/23 06:00
PHST- 2012/09/18 00:00 [received]
PHST- 2013/01/14 00:00 [revised]
PHST- 2013/01/20 00:00 [accepted]
PHST- 2013/02/23 06:00 [entrez]
PHST- 2013/02/23 06:00 [pubmed]
PHST- 2014/01/17 06:00 [medline]
AID - S0197-4580(13)00042-0 [pii]
AID - 10.1016/j.neurobiolaging.2013.01.012 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2013 Jul;34(7):1902-12. doi: 
      10.1016/j.neurobiolaging.2013.01.012. Epub 2013 Feb 19.