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Suppression of MMP-9 expression in brain microvascular endothelial cells (BMVEC) using a gold nanorod (GNR)-siRNA
Supriya D Mahajan1, Ravikumar Aalinkeel, Jessica L Reynolds
1Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University at Buffalo, The State University of New York, Innovation Center, Buffalo, New York 14203, USA. smahajan@buffalo.edu
Abstract:
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.
Insights
Silencing matrix metalloproteinase-9 (MMP-9) with gold nanorod-siRNA nanoplexes increased tight junction proteins in brain endothelial cells. This approach may prevent blood-brain barrier disruption during neuroinflammation.
Area of Science:
- Neuroscience
- Biotechnology
- Cell Biology
Background:
- The blood-brain barrier (BBB) maintains central nervous system homeostasis.
- Matrix metalloproteinase-9 (MMP-9) activation contributes to BBB disruption and neuroinflammation.
- Tight junction (TJ) proteins are crucial for BBB integrity.
Purpose of the Study:
- To investigate if gold nanorod (GNR)-MMP-9 siRNA nanoplexes can modulate TJ protein expression in brain microvascular endothelial cells (BMVECs).
- To determine if gene silencing of MMP-9 impacts BBB permeability.
- To explore a potential therapeutic strategy for preventing BBB dysfunction.
Main Methods:
- BMVECs were transfected with GNR-MMP-9 siRNA nanoplexes.
- Gene and protein expression of TJ proteins (ZO-1, Occludin, Claudin-5) were analyzed.
- The effect of MMP-9 gene silencing on endothelial permeability was assessed.
Main Results:
- Transfection with GNR-MMP-9 siRNA nanoplexes significantly increased gene and protein expression of ZO-1, Occludin, and Claudin-5 in BMVECs.
- MMP-9 gene silencing led to enhanced expression of TJ proteins.
- This suggests a protective effect on BBB integrity.
Conclusions:
- Silencing MMP-9 expression using GNR-siRNA nanoplexes can upregulate TJ proteins in BMVECs.
- This strategy holds promise for preventing BBB disruption caused by MMP-9 activation in neuroinflammatory conditions.
- Targeting MMP-9 offers a potential therapeutic avenue for neurological disorders.
