Adrenomedullin improves the blood-brain barrier function through the expression of claudin-5.
OBJECTIVE
Brain vascular endothelial cells secret Adrenomedullin (AM) has multifunctional biological properties. AM affects cerebral blood flow and blood-brain barrier (BBB) function. We studied the role of AM on the permeability and tight junction proteins of brain microvascular endothelial cells (BMEC).


METHODS
BMEC were isolated from rats and a BBB in vitro model was generated. The barrier functions were studied by measuring the transendothelial electrical resistance (TEER) and the permeability of sodium fluorescein and Evans' blue albumin. The expressions of tight junction proteins were analyzed using immunocytochemistry and immunoblotting.


RESULTS
AM increased TEER of BMEC monolayer dose-dependently. Immunocytochemistry revealed that AM enhanced the claudin-5 expression at a cell-cell contact site in a dose-dependent manner. Immunoblotting also showed an overexpression of claudin-5 in AM exposure.


CONCLUSIONS
AM therefore inhibits the paracellular transport in a BBB in vitro model through claudin-5 overexpression.
Honda
Masaru
M
Department of Neurosurgery, Nagasaki University School of Medicine, Nagasaki, Japan. mahonda-nsu@umin.ac.jp
Nakagawa
Shinsuke
S
Hayashi
Kentaro
K
Kitagawa
Naoki
N
Tsutsumi
Keisuke
K
Nagata
Izumi
I
Niwa
Masami
M
D053607:Adrenomedullin / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D062507:Claudin-5; D017097:Electric Impedance; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
D062507:Claudin-5; C491510:Cldn5 protein, rat; D008565:Membrane Proteins; D053607:Adrenomedullin