期刊
IMMUNOLOGICAL INVESTIGATIONS
卷 41, 期 4, 页码 337-355出版社
TAYLOR & FRANCIS INC
DOI: 10.3109/08820139.2011.604863
关键词
MMP-9; Gold Nano Rods; siRNA; Tight junctions; Gene silencing; BMVEC
类别
资金
- National Institute of Health [RO1CA119397, NIAID-RO1LM009726-01, NIDA K01 DA024577, NIDA-1R21DA030108-01]
- John R. Oishei Foundation
- Kaleida Health Foundation
Inhibition of Matrix metalloproteinase-9 (MMP-9) activity using delivery of short interfering RNA (siRNA) molecules to brain microvascular endothelial cells (BMVECs) that constitute the BBB may have a significant impact on reducing the BBB permeability. Gold nano rods (GNRs) can electrostatically bind with MMP-9 siRNA to form a nanoplex and the uptake of this nanoplex by BMVEC cells can result in suppression of MMP-9 expression. The current study explores if this GNR-MMP-9 siRNA nanoplex gene silencing modulates the expression of tight junction (TJ) proteins in the BMVEC. The endothelial TJ's of the BBB play a critical role in controlling cellular traffic into the central nervous system. We hypothesize that silencing of the MMP-9 gene expression in BMVEC will increase the expression of TJ proteins thereby decrease endothelial permeability. Our results showed a significant increase in the gene and protein expression of TJ proteins: ZO-1, Occludin and Claudin-5 in BMVEC cells that were transfected with the GNRs-siRNA-MMP-9 nanoplex suggesting that BBB disruption, which results from loss of TJ function due to MMP-9 activation during neuroinflammation can be prevented by silencing MMP-9 expression.
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