Endothelial-monocyte-activating polypeptide II increases blood-tumor barrier permeability by down-regulating the expression levels of tight junction associated proteins.
This study was performed to determine whether endothelial-monocyte-activating polypeptide (EMAP) II increases the permeability of the blood-tumor barrier (BTB) in the rat model of C6 glioma, and whether EMAP II opens the BTB by affecting tight junction (TJ) associated proteins zonula occluden-1 (ZO-1), occludin and claudin-5. The rats were divided into eight groups randomly: control group, EMAPII 0h group, EMAPII 0.5h group, EMAPII 1h group, EMAPII 2h group, EMAPII 3h group, EMAPII 6h group and EMAPII 12h group. The BTB permeability was assessed by Evans blue extravasation. The mRNA and protein expressions of ZO-1, occludin, and claudin-5 were determined by reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry assays. The BTB permeability significantly increased after EMAP II injection in different doses (40ng/kg, 80ng/kg and 160ng/kg). The BTB permeability started to increase from 0.5h, reached a peak at 1h, and finally returned to the level of EMAP II 0h group after EMAP II injection at dose of 80ng/kg. The mRNA and protein expression levels of ZO-1, occludin and claudin-5 were significantly decreased after EMAP II injection. This study demonstrates for the first time that EMAP II increases the permeability of BTB selectively, and the possible mechanism is associated with the down-regulation of ZO-1, occludin and claudin-5.
Xie
Hui
H
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning province, 110001, PR China.
Xue
Yi-Xue
YX
Liu
Li-Bo
LB
Liu
Yun-Hui
YH
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology*; D062507:Claudin-5; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005910:Glioma / Q000098:blood supply / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000378:metabolism*; D013997:Time Factors; D062826:Zonula Occludens-1 Protein
D062507:Claudin-5; C491510:Cldn5 protein, rat; D016207:Cytokines; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C077219:small inducible cytokine subfamily E, member 1