Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University at Buffalo, The State University of New York, Innovation Center, Buffalo, New York 14203, USA.
Immunol Invest. 2012;41(4):337-55. doi: 10.3109/08820139.2011.604863. Epub 2011 Aug 24.
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.
抑制基质金属蛋白酶-9（MMP-9）的活性，使用短干扰 RNA（siRNA）分子传递到脑微血管内皮细胞（BMVECs），构成 BBB，可能对降低 BBB 通透性有重大影响。金纳米棒（GNRs）可以与 MMP-9 siRNA 静电结合形成纳米复合物，而 BMVEC 细胞对这种纳米复合物的摄取可能导致 MMP-9 表达的抑制。本研究探讨了这种 GNR-MMP-9 siRNA 纳米复合物基因沉默是否调节 BMVEC 中紧密连接（TJ）蛋白的表达。BBB 的内皮 TJ 在控制细胞进入中枢神经系统的过程中起着关键作用。我们假设 BMVEC 中 MMP-9 基因表达的沉默会增加 TJ 蛋白的表达，从而降低内皮通透性。我们的结果显示，转染 GNRs-siRNA-MMP-9 纳米复合物的 BMVEC 细胞中 TJ 蛋白的基因和蛋白表达显著增加：ZO-1、Occludin 和 Claudin-5，这表明由于 MMP-9 激活导致的 TJ 功能丧失引起的 BBB 破坏，通过沉默 MMP-9 表达可以预防。
