Bioreducible Polymer–delivered siRNA Targeting MMP-9: Suppression of Granulation Tissue Formation after Bare Metallic Stent Placement in a Rat Urethral Model
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- Bioreducible Polymer–delivered siRNA Targeting MMP-9: Suppression of Granulation Tissue Formation after Bare Metallic Stent Placement in a Rat Urethral Model
- Jung-Hoon Park; Jin Hyoung Kim; Eun-Young Kim; Jinoo Kim; Ho-Young Song; Won Jong Kim; Duhwan Lee; Jihong Park; Soohwan Kim
- RADIOLOGY, v.271, no.1, pp.87 - 95
- RADIOLOGICAL SOC NORTH AMERICA
- To evaluate the effectiveness of small interfering RNA
(siRNA) targeting matrix metalloproteinase 9 (MMP-9) in
suppressing granulation tissue formation caused by bare
metallic stent placement in a rat urethral model.
All experiments were approved by the committee of animal
research. In 20 Sprague-Dawley male rats (weight
range, 300–350 g), a self-expanding metallic bare stent
was inserted in the urethra with fluoroscopic guidance.
One group of 10 rats (group A) was treated with MMP-9
siRNA/bioreducible branched polyethylenimine–disulfide
cross-linked–indocyanine green (bioreducible BPEI–SSICG),
while the other group of 10 rats (group B) received
control siRNA/bioreducible BPEI–SS-ICG treatment. All
rats were sacrificed at 4 weeks. The therapeutic effectiveness
of the MMP-9 siRNA/bioreducible BPEI–SS-ICG
complex was assessed by comparing the two results of retrograde
urethrography, histologic examination, and quantification
of MMP-9 by using zymography and Western
blot analysis between the two groups. The Mann-Whitney
U test was used to evaluate differences.
Stent placement was successful in all rats without a single
case of migration at follow-up. Retrograde urethrography
performed 4 weeks after stent placement demonstrated
significantly larger luminal diameters of the urethra
within the stents in group A compared with those in
group B (P = .011). Histologic analysis revealed that the
mean percentage of granulation tissue area (P , .001),
mean number of epithelial layers (P , .001), and mean
thickness of submucosal fibrosis (P , .001) were significantly
decreased in group A compared with group B.
Meanwhile, the mean density of inflammatory cell infiltration
did not significantly differ between the two groups
(P = .184). Quantitative analysis disclosed MMP-9 levels
to be lower in group A relative to group B, indicating positive
inhibition of MMP-9 by MMP-9 siRNA/bioreducible
MMP-9 siRNA/bioreducible BPEI–SS-ICG is effective for
inhibiting granulation tissue formation after bare metallic
stent placement in a rat urethral model.
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