title: Pericyte-derived glial cell line-derived neurotrophic factor increase the expression of claudin-5 in the blood-brain barrier and the blood-nerve barrier.
abstract: The destruction of blood-brain barrier (BBB) and blood-nerve barrier (BNB) has been considered to be a key step in the disease process of a number of neurological disorders including cerebral ischemia, Alzheimer's disease, multiple sclerosis, and diabetic neuropathy. Although glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) facilitate neuronal or axonal regeneration in the brain or peripheral nerves, their action in the BBB and BNB remains unclear. The purpose of the present study was to elucidate whether these neurotrophic factors secreted from the brain or peripheral nerve pericytes increase the barrier function of the BBB or BNB, using our newly established human brain microvascular endothelial cell (BMEC) line or peripheral nerve microvascular endothelial cell (PnMEC) line. GDNF increased the expression of claudin-5 and the transendothelial electrical resistance (TEER) of BMECs and PnMECs, whereas BDNF did not have this effect. Furthermore, we herein demonstrate that the GDNF secreted from the brain and peripheral nerve pericytes was one of the key molecules responsible for the up-regulation of claudin-5 expression and the TEER value in the BBB and BNB. These results indicate that the regulation of GDNF secreted from pericytes may therefore be a novel therapeutic strategy to modify the BBB or BNB functions and promote brain or peripheral nerve regeneration.
authors: Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1, Minamikogushi, Ube, Yamaguchi, 7558505, Japan.
authors: Fumitaka
authors: F
authors: Shimizu
authors: Yasuteru
authors: Y
authors: Sano
authors: Kazuyuki
authors: K
authors: Saito
authors: Masa-aki
authors: MA
authors: Abe
authors: Toshihiko
authors: T
authors: Maeda
authors: Hiroyo
authors: H
authors: Haruki
authors: Takashi
authors: T
authors: Kanda
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D001483:Base Sequence; D001812:Blood-Brain Barrier; D049428:Blood-Nerve Barrier; D015153:Blotting, Western; D002461:Cell Line, Transformed; D062507:Claudin-5; D057167:Claudins / Q000378:metabolism*; D017931:DNA Primers; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D020286:Pericytes / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D057134:Antibodies, Neutralizing; C107466:CLDN5 protein, human; D062507:Claudin-5; D057167:Claudins; D017931:DNA Primers; D051100:Glial Cell Line-Derived Neurotrophic Factor